Clinical trial NCT02739360
Conditions: Lymphoid Malignancies
Sponsor: Gilead Sciences
Start date: 2016-05-04; Completion date: 2017-12-28
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary objective of this study is to provide idelalisib to participants receiving GS-9820 in Gilead-sponsored Study GS-US-315-0102 at the time of study closure.

Detailed description:

Arms: arm 1: Participants will receive idelalisib until unacceptable toxicity, disease progression, study discontinuation, or death occurs.
Interventions: intervention 1: Idelalisib
Intervention descriptions: intervention 1: Idelalisib 150 mg tablet administered orally twice daily

Protocol documents:
SAP_004.pdf: 
Study Title: 
Name of Test Drug: 
Study N urn ber: 
Protocol Version (Date): 
Analysis Type: 
Analysis Plan Version: 
Analysis Plan Date: 
Analysis Plan Author(s): 
(rJ GILEAiJ 
STATISTICAL ANALYSIS PLAN 
An Open-Label, Roll-Over Study to Provide Idelalisib to 
Subjects Previously Treated with the Investigational PI3Ko 
Inhibitor, GS-9820 
Idelalisib 
GS-US-3 13-2120 
Amendment 3 (04 November 2016) 
Final Analysis 
1.0 
21 March 2018 
PPD 
CONFIDENTIAL AND PROPRIETARY INFORMATION 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF ABBREVIATIONS........................................................................................................................................4
1.
INTRODUCTION ................................................................................................................................................5
1.1.
Study Objectives ......................................................................................................................................5
1.2.
Study Design............................................................................................................................................5
1.3.
Sample Size and Power............................................................................................................................5
2.
TYPE OF PLANNED ANALYSIS ......................................................................................................................6
2.1.
Interim Analyses ......................................................................................................................................6
2.2.
Final Analysis ..........................................................................................................................................6
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES..............................................................................7
3.1.
Analysis Sets............................................................................................................................................7
3.1.1.
Safety Analysis Set.................................................................................................................7
3.2.
Subject Grouping .....................................................................................................................................7
3.3.
Strata and Covariates................................................................................................................................7
3.4.
Examination of Subject Subgroups..........................................................................................................7
3.5.
Multiple Comparisons..............................................................................................................................7
3.6.
Missing Data and Outliers........................................................................................................................7
3.6.1.
Missing Data ..........................................................................................................................7
3.6.2.
Outliers...................................................................................................................................7
3.7.
Data Handling Conventions and Transformations ...................................................................................8
3.8.
Analysis Visit Windows...........................................................................................................................8
3.8.1.
Definition of Study Day .........................................................................................................8
3.8.2.
Analysis Visit Windows.........................................................................................................8
4.
SUBJECT DISPOSITION ....................................................................................................................................9
4.1.
Subject Enrollment and Disposition.........................................................................................................9
4.2.
Extent of Study Drug Exposure ...............................................................................................................9
4.3.
Protocol Deviations..................................................................................................................................9
5.
BASELINE CHARACTERISTICS....................................................................................................................10
5.1.
Demographics ........................................................................................................................................10
5.2.
Medical History......................................................................................................................................10
6.
EFFICACY ANALYSES ...................................................................................................................................11
7.
SAFETY ANALYSES........................................................................................................................................12
7.1.
Adverse Events and Deaths....................................................................................................................12
7.1.1.
Adverse Event Dictionary ....................................................................................................12
7.1.2.
Adverse Event Severity........................................................................................................12
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................12
7.1.4.
Serious Adverse Events........................................................................................................12
7.1.5.
Treatment-Emergent Adverse Events...................................................................................12
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................13
7.2.
Laboratory Evaluations ..........................................................................................................................13
7.2.1.
Graded Laboratory Values ...................................................................................................13
7.2.2.
Liver-related Laboratory Evaluations...................................................................................14
7.3.
Prior and Concomitant Medications.......................................................................................................14
7.3.1.
Prior Medications .................................................................................................................14


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7.3.2.
Concomitant Medications.....................................................................................................14
7.4.
Other Safety Measures ...........................................................................................................................15
7.4.1.
Pregnancy.............................................................................................................................15
7.5.
Changes From Protocol-Specified Safety Analyses...............................................................................15
8.
SOFTWARE.......................................................................................................................................................16
9.
SAP REVISION..................................................................................................................................................17
10.
APPENDIX 1 SCHEDULE OF ASSESSMENTS .............................................................................................18


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BMI
body mass index
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
DMC
data monitoring committee
eCRF
electronic case report form
HLGT
high-level group term
HLT
high-level term
LLT
lower-level term
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
PT
preferred term
SAE
serious adverse event
SAP
statistical analysis plan
SOC
system organ class
StD
standard deviation
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-313-2120. This SAP is based on Protocol GS-US-313-2120 Amendment 3
dated 4 November 2016 and the electronic case report form (eCRF). The SAP will be finalized 
before database finalization. Any changes made after finalization of the SAP will be documented 
in the CSR.
1.1.
Study Objectives
The primary objective of this study is as follows:

To provide idelalisib, a marketed PI3Kδ inhibitor, in lieu of GS-9820, an investigational 
second generation PI3Kδ inhibitor, to subjects receiving GS-9820 in Study GS-US-315-0102 
at the time of study closure who have had objective evidence of clinical benefit defined as at 
least stable disease on imaging assessed by the IRC and no toxicities prior to enrollment in 
this study that would preclude initiating therapy with idelalisib. Idelalisib and GS-9820 are 
both in the class of agents that inhibit PI3Kδ and as such this exchange of class for class 
agent is warranted and acceptable.
1.2.
Study Design
This study is an open-label, rollover study to provide idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure.
1.3.
Sample Size and Power
There is no formal hypothesis to be tested in this study; therefore, no formal sample size 
calculation was performed.
A total of 3 subjects were enrolled in Study GS-US-313-2120.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
This study does not have a data monitoring committee (DMC). Therefore, no analyses will be 
conducted for the DMC.
2.2.
Final Analysis
After all subjects have completed the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized, the final analysis of 
the data will be performed.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
By-subject listings will be presented for all subjects in the Safety Analysis Set and sorted by 
subject identification (ID) number, visit date, and time (if applicable). Data collected on log 
forms, such as AEs, will be presented in chronological order within the subject. Age, sex at birth, 
race, and ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The analysis set will be identified and included as a subtitle of each
listing.
3.1.1.
Safety Analysis Set
The Safety Analysis Set includes all subjects who took at least 1 dose of study drug. This is the 
primary analysis set for safety analyses.
3.2.
Subject Grouping
Not Applicable.
3.3.
Strata and Covariates
This study does not use a stratified randomization schedule when enrolling subjects. 
No covariates will be included in safety analyses.
3.4.
Examination of Subject Subgroups
There are no prespecified subject subgroupings for safety analyses.
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be made, because no formal statistical testing will be 
performed in this study.
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified.
3.6.2.
Outliers
All data will be included in the data analysis.


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3.7.
Data Handling Conventions and Transformations
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. For screen failures, the date the informed consent was signed will be 
used for age calculation. If only the birth year is collected on the CRF, “01 July” will be used for 
the unknown birth day and month for the purpose of age calculation. If only birth year and month 
are collected, “01” will be used for the unknown birth day.
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of study drug and derived as follows:

For postdose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.  
3.8.2.
Analysis Visit Windows
The nominal visit as recorded on the eCRF will be used. 


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
The following by-subject listing will be provided by subject ID number in ascending order:

Reasons for premature study drug discontinuation
4.2.
Extent of Study Drug Exposure
A by-subject listing of study drug administration will be provided by subject ID number 
(in ascending order) and visit (in chronological order).
4.3.
Protocol Deviations
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. A by-subject listing will be provided for those subjects with important protocol 
deviations.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics
A by-subject demographic listing, including age, sex, race, and ethnicity, will be provided by 
subject ID number in ascending order.
5.2.
Medical History
Medical history will be collected at screening for general conditions (ie, conditions not specific 
to the disease being studied).
General medical history data will not be coded, but will be listed only.


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6.
EFFICACY ANALYSES
No efficacy analyses will be conducted for this study.


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of Medical 
Dictionary for Regulatory Activities (MedDRA). System organ class (SOC), high-level group 
term (HLGT), high-level term (HLT), preferred term (PT), and lower-level term (LLT) will be 
provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to Common 
Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. The severity grade of events for 
which the investigator did not record severity will be categorized as “missing” for data listings.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s
choice, not that of the medical monitor. Events for which the investigator did not record 
relationship to study drug will be shown as missing in by-subject data listings.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Drug Safety and 
Public Health Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset is the same as or after the month and year (or year) of the first dosing date of 
study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Deaths
All AEs will be listed based on the Safety Analysis Set.
7.2.
Laboratory Evaluations
By-subject listings of laboratory data will be provided by subject ID number and visit in 
chronological order for serum chemistry based on the Safety Analysis Set. When values are 
below the LOQ, they will be listed as such, and hemolized test results will be included. Values 
falling outside of the relevant reference range and/or having a severity grade of 1 or higher on 
the CTCAE severity grade will be flagged in the data listings, as appropriate.
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date/time of first dose of study drug.
7.2.1.
Graded Laboratory Values
CTCAE, Version 4.03, will be used to assign toxicity grades (0 to 4) to laboratory results for 
analysis. Grade 0 includes all values that do not meet the criteria for an abnormality of at least 
Grade 1. For laboratory tests with criteria for both increased and decreased levels, analyses for 
each direction (ie, increased, decreased) will be presented separately. 
7.2.1.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days for subjects who permanently discontinued study drug. If the 
relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed 
within the time frame specified above will be considered treatment emergent.


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7.2.2.
Liver-related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined using the following 
laboratory test values for postbaseline measurements:

Aspartate aminotransferase (AST): (a) > 3 times of the upper limit of reference range  
(ULN); (b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x ULN

Alanine aminotransferase (ALT): (a) > 3 x ULN; (b) > 5 x ULN; (c) > 10 x ULN; 
(d) > 20 x ULN

Total bilirubin: (a) > 1.5 x ULN, (b) > 2 x ULN

AST or ALT > 3 x ULN: (a) total bilirubin> 1.5 x ULN; (b) total bilirubin > 2 x ULN
For individual laboratory tests, subjects will be counted once based on the most severe 
postbaseline values. For both the composite endpoint of AST or ALT and total bilirubin, subjects 
will be counted once when the criteria are met at the same postbaseline visit date. A listing of 
subjects who met at least 1 of the above criteria will be provided.
7.3.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
7.3.1.
Prior Medications
Prior medications are defined as any medications taken before a subject took the first dose of 
study drug. 
For the purposes of analysis, any medication with a start date prior to the first dosing date of 
study drug will be included in the prior medication summary regardless of when the stop date is. 
If a partial start date is entered, the medication will be considered prior unless the month and 
year (if day is missing) or year (if day and month are missing) of the start date are after the first 
dosing date.
7.3.2.
Concomitant Medications
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to or on the last dosing date of study drug will be considered concomitant 
medications. Medications started and stopped on the same day as the first dosing date or the last 
dosing date of study drug will also be considered concomitant. Medications with a stop date prior 
to the date of first dosing date of study drug or a start date after the last dosing date of study drug 
will be excluded from the concomitant medication summary. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
prior to the date of first study drug administration will be excluded from the concomitant 


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medication summary. If a partial start date is entered, any medication with the month and year 
(if day is missing) or year (if day and month are missing) after the study drug stop date will be 
excluded from the concomitant medication summary. Medications with completely missing start 
and stop dates will be considered as a concomitant medication.
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order.
7.4.
Other Safety Measures
7.4.1.
Pregnancy
A data listing will be provided for subjects who became pregnant during the study.
7.5.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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9.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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10.
APPENDIX 1 SCHEDULE OF ASSESSMENTS
Period
Screen
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15+
End of 
study
Week
-4
0
2
4
6
8
10
12
14
16
18
20
22
24
Q4 
weeks
Q12 
weeks
Study Day
Within
-28 days
1
14
28
42
52
70
84
98
112
126
140
154
168
Visit Window
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±7
±7
Informed consent
X
Serum -HCGa
X
Pneumococcal, Hib, Tetanus titers
X
ALT/AST/total bilirubin
X
X
X
X
X
X
X
X
X
Urine pregnancy testa
X
X
X
X
X
X
X
X
ANCb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CMV surveillance
X
X
X
X
X
X
X
Xc
Immune Monitoring
X
X
X
X
X
X
Assess adverse events and SAEsd
X
X
X
X
X
X
X
X
Record concomitant 
medicationse
X
X
X
X
X
X
X
X
Idelalisib dispensing/accounting
X
X
X
X
X
X
X
X
Investigator response 
assessmentf
X
X
X
X
X
X
X
X
Abbreviations: -HCG=beta human chorionic gonadotropin, ALT=alanine aminotransferase, AST=aspartate aminotransferase, Hib = Haemophilus Influenzae Type B
a
For women of child bearing potential; Serum -HCGto be collected to be collected at screening, urine pregnancy test to be collected at visits from first dose of idelalisib to EOS
b
Absolute neutrophil count (ANC) will be monitored at least every two weeks for the first 24 weeks of idelalisib treatment
c
CMV surveillance must be conducted approximately every 4 weeks throughout the course of idelalisib treatment
d
For an AE of Diarrhea/Colitis: 1) Obtain history of onset and duration of diarrhea, including description of number of stools and stool composition, travel history, dietary 
changes and a medication review to identify possible diarrheogenic agents and 2) Perform physical examination including assessment for fever, dizziness, abdominal 
pain/cramping, and weakness
e
Concomitant medications only collected if it is related to an AE
f
Record investigator response assessment if obtained per standard of care

Prot_003.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Director 
or Clinical Program 
Manager: 
Gilead Medical 
Monitor: 
Protocol Version/Date: 
(!') GILEAU 
CLINICAL STUDY PROTOCOL 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Ko Inhibitor, GS-9820 
Gilead Sciences, Inc. 
199 East Blaine Street 
Seattle, W A 98102 
N/A 
2015-005766-39 
Lymphoid Malignancies 
GS-US-313-2120 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Original: 
Amendment 1: 
Amendment 2: 
Amendment 3: 
PPD 
PPD 
PPD 
Mario Marcondes 
PPD 
PPD 
05 Januaty 2016 
28 Mru·ch 2016 
26 August 2016 
04 November2016 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this document, particulru-Iy unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The infonnation is only to be used by you in 
connection with authorized clinical studies of the investigational dmg described in the protocol. 
You will not disclose any of the infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessa1y to obtain infmmed consent from those 
persons to whom the dmg may be administered. 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF IN-TEST FIGURES.......................................................................................................................................4
PROTOCOL SYNOPSIS ..............................................................................................................................................5
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS......................................................................8
1.
INTRODUCTION ..............................................................................................................................................10
1.1.
Background ............................................................................................................................................10
1.2.
Idelalisib.................................................................................................................................................10
1.3.
Rationale for This Study ........................................................................................................................11
1.4.
Benefit/Risk Assessment for the Study..................................................................................................11
1.5.
Compliance ............................................................................................................................................11
2.
OBJECTIVES.....................................................................................................................................................12
3.
STUDY DESIGN................................................................................................................................................13
3.1.
Endpoints ...............................................................................................................................................13
3.2.
Study Design..........................................................................................................................................13
3.3.
Study Treatments ...................................................................................................................................13
3.4.
Duration of Treatment............................................................................................................................13
3.5.
Discontinuation Criteria.........................................................................................................................13
3.6.
Source Data............................................................................................................................................14
3.7.
Biomarker Testing..................................................................................................................................14
4.
SUBJECT POPULATION..................................................................................................................................15
4.1.
Number of Subjects and Subject Selection ............................................................................................15
4.2.
Inclusion Criteria....................................................................................................................................15
4.3.
Exclusion Criteria...................................................................................................................................15
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................17
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................17
5.2.
Description and Handling of Study Treatments .....................................................................................17
5.2.1.
Formulation..........................................................................................................................17
5.2.2.
Packaging and Labeling .......................................................................................................17
5.2.3.
Storage and Handling...........................................................................................................17
5.2.4.
Dosage and Administration of Idelalisib..............................................................................17
5.2.5.
Dispensing............................................................................................................................18
5.2.6.
Premedication.......................................................................................................................18
5.2.7.
Administration Instructions..................................................................................................18
5.2.8.
Dosing Schedule...................................................................................................................18
5.2.9.
Dose Levels..........................................................................................................................18
5.2.10.
Idelalisib Dose Adjustments.................................................................................................19
5.3.
Prior and Concomitant Medications.......................................................................................................23
5.3.1.
Anticancer or Experimental Therapies Other than Investigational 
Treatments............................................................................................................................23
5.3.2.
Antibiotics/ PJP Prophylaxis................................................................................................23
5.3.3.
Antidiarrheals.......................................................................................................................25
5.3.4.
Corticosteroids .....................................................................................................................25
5.3.5.
Granulocyte Colony-Stimulating Factors and Erythropoietin..............................................25
5.3.6.
Drugs that Alter CYP3A-Dependent Metabolism................................................................25


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5.3.7.
Drugs that undergo CYP3A-Dependent Metabolism...........................................................26
5.3.8.
Immunization .......................................................................................................................26
5.3.9.
Ultraviolet Exposure ............................................................................................................26
5.3.10.
Surgery .................................................................................................................................26
5.4.
Accountability for Idelalisib...................................................................................................................27
5.4.1.
Overdose Precautions...........................................................................................................27
5.4.2.
Inadvertent Exposure and Spill Precautions.........................................................................27
5.4.3.
Investigational Medicinal Product Return or Disposal.........................................................28
5.5.
Discontinuation from Study ...................................................................................................................28
6.
STUDY PROCEDURES ....................................................................................................................................29
6.1.
Subject Enrollment.................................................................................................................................29
6.1.1.
Subject Recruitment .............................................................................................................29
6.1.2.
Subject Compensation for Participation...............................................................................29
6.1.3.
Screening Visit .....................................................................................................................29
6.2.
Treatment Assessments..........................................................................................................................29
6.2.1.
Clinical Evaluation...............................................................................................................30
6.2.2.
Laboratory Assessments.......................................................................................................30
6.3.
End of Study...........................................................................................................................................31
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................34
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................34
7.1.1.
Adverse Events.....................................................................................................................34
7.1.2.
Serious Adverse Events........................................................................................................34
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................35
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................35
7.2.1.
Assessment of Causality for Idelalisib and Procedures........................................................35
7.2.2.
Assessment of Severity ........................................................................................................36
7.3.
Evaluation, Intervention, and Drug Discontinuation for Specific Adverse Events or 
Conditions ..............................................................................................................................................37
7.3.1.
Dermatological Events (Idelalisib).......................................................................................37
7.3.2.
Gastrointestinal Events.........................................................................................................37
7.3.3.
Hepatic Events......................................................................................................................38
7.3.4.
Hematological and Immunological Events...........................................................................39
7.3.5.
Pulmonary Events ................................................................................................................39
7.3.6.
Secondary Malignancies.......................................................................................................40
7.3.7.
Tumor Lysis Syndrome........................................................................................................40
7.4.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................40
7.4.1.
Serious Adverse Event (eSAE) Reporting Process ..............................................................41
7.5.
Gilead Reporting Requirements.............................................................................................................41
7.5.1.
Reporting of Adverse Events Relating and Other Anticipated Medical 
Events in the Study Population ............................................................................................42
7.5.2.
Toxicity Management...........................................................................................................42
7.6.
Special Situations Reports......................................................................................................................42
7.6.1.
Definitions of Special Situations..........................................................................................42
7.6.2.
Instructions for Reporting Special Situations.......................................................................43
8.
STATISTICAL CONSIDERATIONS................................................................................................................45
8.1.
Analysis Objectives................................................................................................................................45
8.2.
Safety Endpoints ....................................................................................................................................45
8.3.
Analysis Sets..........................................................................................................................................45
8.4.
Analysis Methods...................................................................................................................................45


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8.5.
Adverse Events.......................................................................................................................................45
9.
RESPONSIBILITIES..........................................................................................................................................46
9.1.
Investigator Responsibilities ..................................................................................................................46
9.1.1.
Good Clinical Practice..........................................................................................................46
9.1.2.
Independent Ethics Committee (IEC) Review and Approval...............................................46
9.1.3.
Informed Consent.................................................................................................................46
9.1.4.
Confidentiality......................................................................................................................47
9.1.5.
Study Files and Retention of Records ..................................................................................47
9.1.6.
Case Report Forms...............................................................................................................48
9.1.7.
Drug Accountability and Return ..........................................................................................49
9.1.8.
Inspections............................................................................................................................49
9.1.9.
Protocol Compliance............................................................................................................49
9.2.
Sponsor Responsibilities ........................................................................................................................49
9.2.1.
Protocol Modifications.........................................................................................................49
9.2.2.
Communications with Regulatory Authorities.....................................................................50
9.2.3.
Study Report and Publications .............................................................................................50
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................50
9.3.1.
Payment Reporting...............................................................................................................50
9.3.2.
Access to Information for Monitoring..................................................................................51
9.3.3.
Access to Information for Auditing or Inspections ..............................................................51
9.3.4.
Study Discontinuation..........................................................................................................51
10.
REFERENCES ...................................................................................................................................................52
11.
APPENDICES ....................................................................................................................................................55
Appendix 1.
Investigator Signature Page....................................................................................................56
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................57
LIST OF IN-TEXT TABLES
Table 5-1.
Idelalisib Dose Levels ............................................................................................................19
Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}.....................................................20
Table 6-1.
Schedule of Study Procedures................................................................................................33
Table 7-1.
Grading of Adverse Event Severity........................................................................................36
LIST OF IN-TEST FIGURES
Figure 7-1.
Kaplan-Meier Time to Diarrhea or Colitis .............................................................................38


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
199 East Blaine Street
Seattle, WA 98102
Study Title: 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Kδ Inhibitor, GS-9820
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
Not Applicable
2015-005766-39
Study Centers 
Planned:
2 centers in the Netherlands
Objectives:
The primary objective of this study is as follows:

To provide open-label idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure who have had
objective evidence of clinical benefit defined as at least stable 
disease on imaging assessed by an independent review committee 
(IRC) and no toxicities prior to enrollment in this study that 
would preclude initiating therapy with idelalisib. Idelalisib and 
GS-9820 are both in the class of agents that inhibit PI3Kδ and as 
such this exchange of class for class agent is warranted and 
acceptable.
Study Design:
This study is an open-label, rollover study to provide idelalisib to 
subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure.
Number of Subjects 
Planned:
Approximately 6 subjects
Target Population:
Subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure who have objective evidence of clinical benefit defined 
as at least stable disease on imaging assessed by the IRC at final 
response assessment prior to enrollment in this study.


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Duration of 
Treatment:
Subjects will be treated until withdrawal from study drug, progressive 
disease, intolerable study drug-related toxicity, pregnancy, substantial 
noncompliance with study procedures, or study discontinuation.
Idelalisib administration should only be continued in subjects with a 
positive benefit-risk profile assessment as per the investigator.
Diagnosis and Main 
Eligibility Criteria:
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be 
eligible for participation in this study:
1) Receiving GS-9820 in Study GS-US-315-0102 with objective 
evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC at the time of Study GS-US-315-0102
closure
2) For female subjects of childbearing potential, willingness to use a 
protocol recommended method of contraception during 
heterosexual intercourse from the signing of informed consent 
throughout the study treatment period and up to 30 days from the 
last dose of idelalisib (see Appendix 2)
3) For male subjects of reproductive potential having intercourse 
with females of childbearing potential, willing to use a protocol 
recommended method of contraception during heterosexual 
intercourse and to refrain from sperm donation throughout the 
study treatment period and for 90 days following discontinuation 
of idelalisib (see Appendix 2)
4) Willingness to comply with scheduled visits, drug administration 
plan, imaging studies, laboratory tests, other study procedures, 
and study restrictions, including mandatory prophylaxis for 
Pneumocystis jirovecii pneumonia (PJP). Note: Psychological, 
social, familial, or geographical factors that might preclude 
adequate study participation should be considered.
5) Evidence of a personally signed informed consent indicating that 
the subject is aware of the neoplastic nature of their disease and 
has been informed of the procedures to be followed, the 
experimental nature of the therapy, alternatives, potential benefits, 
possible side effects, potential risks and discomforts, and other 
pertinent aspects of study participation.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not
eligible to be enrolled in this study:
1) Known hypersensitivity or intolerance to any of the active 
substances or excipients in the formulation of idelalisib.


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2) Toxicities that would preclude initiating therapy with idelalisib 
prior to enrollment (eg, history of drug-induced pneumonitis, 
ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding
5) Ongoing infection, treatment, or prophylaxis for CMV within the 
past 28 days.
Study Procedures/
Frequency:
All subjects will receive idelalisib 150 mg taken orally, twice per day 
(BID) continuously. Subjects will undergo disease assessments and 
receive medical care per institutional standards of care.
Test Product, Dose, 
and Mode of 
Administration:
Idelalisib: 150 mg taken orally BID starting on Day 1 and 
administered continuously thereafter.
Reference Therapy, 
Dose, and Mode of 
Administration:
None
Criteria for 
Evaluation:
Safety:
Overall safety profile characterized by the type, frequency, severity, 
timing of onset, duration, and relationship to study therapy of ≥Grade 
3 adverse events (AEs), serious adverse events (SAEs), and deaths.
Efficacy:
Investigator response assessments
Statistical Methods:
Safety will be assessed by incidence of ≥ Grade 3 AEs, SAEs, and 
deaths. Efficacy will be evaluated by investigator response 
assessments. Both safety and efficacy will be assessed using data 
collected from subjects who received at least 1 dose of idelalisib. All 
analyses will be limited to descriptive summaries and listings.
Sample Size:
Up to 6 subjects
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
-HCG
beta human chorionic gonadotropin
BID
bis in die (twice daily)
CFR
Code of Federal Regulations
CLL
chronic lymphocytic leukemia
CRO
contract research organization
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DSPH
Drug Safety and Public Health
eCRF
electronic case report form
EOS
end of study
EU
European Union
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
G-CSF
granulocyte colony-stimulating factor
GCP
good clinical practice
GM-CSF
granulocyte-macrophage colony-stimulating factors
HLT
High-Level Term
HMG-CoA
3-hydroxy-3-methyl-glutaryl-Coenzyme A
IB
investigator’s brochure
ICH
International Conference on Harmonisation
iNHL
indolent non-Hodgkin lymphoma
IEC
independent ethics committee
IUD
intrauterine device
MCL
mantle cell lymphoma
NHL
non-Hodgkin lymphoma
PI3K
phosphatidylinositol 3-kinase
PDE5
phosphodiesterase-5
PJP
Pneumocystis jirovecii pneumonia
SAE
serious adverse event
SJS
Stevens-Johnson Syndrome
SOC
system organ class


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SOP
standard operating procedure
SADR
serious adverse drug reaction
SUSAR
suspected unexpected serious adverse reactions
TEN
Toxic Epidermal Necrolysis
ULN
upper limit of normal


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1.
INTRODUCTION
1.1.
Background
B-cell lymphoid malignancies comprise the most common hematological malignancies 
{Surveillance Epidemiology and End Results (SEER) Program 2011}. These cancers arise from 
the accumulation of monoclonal B lymphocytes in lymph nodes and often in organs such as 
blood, bone marrow, lymph nodes, spleen, and liver. Among the variants of these cancers are 
non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), indolent 
non Hodgkin lymphoma (iNHL), and mantle cell lymphoma (MCL), as well as chronic 
lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL). These disorders are characterized 
by lymphadenopathy that is frequently disturbing for patients and can sometimes induce life 
threatening organ dysfunction; patients may also have constitutional symptoms (fevers, night 
sweats, and/or weight loss) and fatigue {Diehl et al 2004, Dighiero et al 2008, Salles 2007, 
Williams et al 2010}. 
The goal of therapy for these diseases is to induce tumor regression and delay tumor progression 
in order to control disease-related complications and potentially extend life. Patients who require 
treatment are commonly given chemotherapeutic and/or immunotherapeutic agents {Eichhorst et 
al 2010, Friedberg 2011, Gribben et al 2011, Hoppe et al 2008, Jost 2007, Zelenetz et al 2011}. 
Among patients with iNHL, CLL, and MCL, front line combination therapies can be effective in 
providing durable remissions {Hallek et al 2010, Lenz et al 2005, Recher et al 2011, Santoro et 
al 1987, Schulz et al 2007}. In DLBCL and HL, such front-line regimens can be curative in the 
majority of patients {Kuruvilla 2009, Recher et al 2011, Santoro et al 1987}. However, most 
treated patients with iNHL, CLL, and MCL will eventually experience disease relapse. Some 
patients with DLBCL or HL will experience recurrent disease even with initial induction therapy 
and later salvage therapy. For any of these cancers, further sequential therapies are given in an 
attempt to control disease manifestations. Despite use of agents with differing mechanisms of 
action, progressive resistance to treatment develops. Patients with progressive disease have a 
poor prognosis; median survival for these groups of patients is generally ≤2 years {Di Bella et al 
2010, Friedberg 2011, Goy et al 2009, Hess et al 2009, Keating et al 2002, Moskowitz et al 2009, 
Wierda et al 2010}. Novel mechanisms of action are needed to offer additional treatment options 
for patients with lymphoid malignancies who are experiencing progressive lymphadenopathy or 
symptoms due to disease progression.
1.2.
Idelalisib
Idelalisib (Zydelig®) was first approved in the United States on July 23, 2014 for the treatment 
of relapsed CLL, follicular lymphoma (FL), and small lymphocytic lymphoma (SLL), followed 
by approval in the EU on September 18, 2014 (centrally authorized). To date, Zydelig is 
currently approved in 37 countries. Refer to local labeling for the approved indication 
statements.


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Idelalisib is a potent competitive inhibitor of the adenosine triphosphate (ATP) binding site of 
the phosphatidylinositol 3 kinase (PI3K) p110δ catalytic domain, which has been shown to be 
prominently expressed in cells of hematopoietic origin {Okkenhaug et al 2003, Vanhaesebroeck 
et al 2005}. The effects of p110δ on lymphocyte activation/function, cellular proliferation, and 
protection from apoptosis provide the rationale for targeting this isoform as a therapy for 
hematologic malignancies.
Further details on the preclinical pharmacology, toxicology, metabolism and pharmacokinetics 
(PK) of idelalisib can be found in the idelalisib Investigator’s Brochure (IB).
1.3.
Rationale for This Study
Study GS-US-315-0102 is being conducted to evaluate the safety and efficacy of GS-9820, a 
second generation PI3Kδ inhibitor in subjects with iNHL, DLBCL, MCL, HL, or CLL. GS-9820 
was anticipated to offer similar efficacy to idelalisib in lymphoid malignancies while offering a 
more favorable safety profile than idelalisib. The development of GS-9820 has been 
discontinued by Gilead Sciences due to demonstration of a similar safety profile to idelalisib. 
Manufacture of the investigational agent GS-9820 has been discontinued, and will no longer be 
available to the ongoing subjects in Study GS-US-315-0102.  
This rollover study provides access to idelalisib for eligible subjects receiving GS-9820 in Study 
GS-US-315-0102 at the time of study closure who have had objective evidence of clinical benefit 
defined as at least stable disease on imaging assessed by the independent review committee 
(IRC) and no toxicities prior to enrollment in this study that would preclude initiating therapy 
with idelalisib.  Subjects will be allowed to receive treatment on this study until unacceptable 
toxicity, progressive disease, study withdrawal, or death occurs.
1.4.
Benefit/Risk Assessment for the Study
Subjects enrolled in this study have a serious life-threatening disease, with limited treatment 
options. Without treatment their disease will progress and ultimately be fatal. Transitioning 
subjects from GS-9820 to idelalisib, a similar agent in class that has shown proof of clinical 
activity and has received regulatory approval for the treatment of relapsed CLL and iNHL 
{Gilead Sciences Limited 2015}, is rational as described in Section 1.3 of this protocol; 
therefore, subjects enrolled in this study may derive clinical benefit defined as an improvement 
in disease control such as response to study treatment. The risks that may accompany study 
treatment are related to the identified and potential toxicities of treatment with idelalisib and are 
described in Section 5 of this protocol and in the ICF. The management of these toxicities is 
described in Table 5-2. Taken together, there is a positive benefit/risk for initiating study 
treatment with idelalisib in subjects previously treated with GS-9820.
1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To provide idelalisib, a marketed PI3Kδ inhibitor, in lieu of GS-9820, an investigational 
second generation PI3Kδ inhibitor, to subjects receiving GS-9820 in Study GS-US-315-0102
at the time of study closure who have had objective evidence of clinical benefit defined as at 
least stable disease on imaging assessed by the IRC and no toxicities prior to enrollment in 
this study that would preclude initiating therapy with idelalisib. Idelalisib and GS-9820 are 
both in the class of agents that inhibit PI3Kδ and as such this exchange of class for class 
agent is warranted and acceptable.


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3.
STUDY DESIGN
3.1.
Endpoints
There is no primary endpoint of this study.
3.2.
Study Design
This study is an open-label, rollover study to provide idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure.
3.3.
Study Treatments
All subjects will receive idelalisib 150 mg taken orally, twice per day (BID) continuously. 
3.4.
Duration of Treatment
Treatment will continue until unacceptable toxicity, disease progression, study discontinuation 
(outlined below), or death occurs.
3.5.
Discontinuation Criteria
Subjects may be withdrawn from the study under the following circumstances:

The subject withdraws consent to participate in the study

The subject permanently discontinues idelalisib treatment for any reason

The subject experiences a toxicity that necessitates permanent discontinuation of idelalisib
treatment

The subject has progressive disease 

The subject does not comply with the requirements of the protocol (eg initiation of a 
non-protocol anti-tumor treatment)

Gilead, a regulatory agency, or an independent ethics committee (IEC) discontinues the study
The reason for withdrawal will be recorded in the eCRF.


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3.6.
Source Data
Electronic data (ie, diagnostic machines that transcribe data directly to a database, or data entered 
directly into an Electronic Medical Record system) is considered source data, provided the data 
is not recorded directly on the CRF/eCRF, and provided there is a clear audit trail in the 
electronic record(s). No data will be recorded directly on the CRF/eCRF, and any data recorded 
directly on the CRF/eCRF will not be considered source data.
3.7.
Biomarker Testing
There will be no biomarker testing in this study.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 6 subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure are anticipated.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Receiving GS-9820 in Study GS-US-315-0102 with objective evidence of clinical benefit 
defined as at least stable disease on imaging assessed by the IRC at the time of Study 
GS-US-315-0102 closure
2) For female subjects of childbearing potential, willingness to use a protocol recommended 
method of contraception during heterosexual intercourse from the signing of informed 
consent throughout the study treatment period and up to 30 days from the last dose of 
idelalisib (see Appendix 2)
3) For male subjects of reproductive potential having intercourse with females of childbearing 
potential, willing to use a protocol recommended method of contraception during 
heterosexual intercourse and to refrain from sperm donation throughout the study treatment 
period and for 90 days following discontinuation of idelalisib (see Appendix 2)
4) Willingness to comply with scheduled visits, drug administration plan, imaging studies, 
laboratory tests, other study procedures, and study restrictions, including mandatory 
prophylaxis for Pneumocystis jirovecii pneumonia (PJP). Note: Psychological, social, 
familial, or geographical factors that might preclude adequate study participation should be 
considered.
5) Evidence of a personally signed informed consent indicating that the subject is aware of the 
neoplastic nature  of their disease and has been informed of the procedures to be followed, 
the experimental nature of the therapy , alternatives, potential benefits, possible side effects, 
potential risks and discomforts, and other pertinent aspects of study participation.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not eligible to be enrolled in this 
study:
1) Known hypersensitivity or intolerance to any of the active substances or excipients in the 
formulation of idelalisib.


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2) Toxicities that would preclude initiating therapy with idelalisib prior to enrollment
(eg history of drug-induced pneumonitis, ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding.
5) Ongoing infection, treatment, or prophylaxis for CMV within the past 28 days.


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5. 
INVESTIGATIONAL MEDICINAL PRODUCTS 
5.1. 
Randomization, Blinding and Treatment Codes 
The study is open-label and non-randomized. 
5.2. 
Description and Handling of Study Treatments 
5.2.1. 
Formulation 
Final 
Amendment 3 
Idelalisib 150 mg tablets aTe pink, oval-shaped and debossed with ''GSI' ' on one side and 
" 150" on the other. The 100 mg tablets are orange, oval-shaped and debossed with "GSI" on 
one side and '' 100'' on the other. All tablets ru·e film-coated, and include the following inactive 
exci ients: PPD 
5.2.2. 
Packaging and Labeling 
Idelalisib tablets, 150 mg or 100 mg, ru·e packaged in white, high density polyethylene (HDPE) 
bottles. Each bottle contains 60 tablets and polyester packing material. Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an induction-
sealed and aluminum-faced liner. 
Idelalisib to be distributed to centers in the US and other pruticipating countries shall be labeled 
to meet applicable requirements of the United States Food and Drug Adtninistration (FDA), EU 
Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal Products), 
ruHJ/or other local regulations. 
5.2.3. 
Storage and Handling 
Idelalisib should be stored at controlled room temperature of 25°C (77°F); excursions ru·e 
pennitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the 
label. Until dispensed to the subjects, all bottles of study dtugs should be stored in a securely 
locked ru·ea, accessible only to authorized site personnel. 
To ensure the stability and proper identification, study d.t·ug should not be stored in a container 
other than the container in which they were supplied. Consideration should be given to handling, 
preparation, and disposal tln·ough measures that minimize drug contact with the body. Appropriate 
precautions should be followed to avoid direct eye contact or exposure when handling. 
5.2.4. 
Dosage and Administration of Idelalisib 
Idelalisib f01mulated drug product of 100 and 150 mg strengths has been manufactured for 
clinical trials and will be provided to the subject to be taken at home. Subjects should be 
instructed to take the doses with water. Idelalisib may be taken with or without food. Missed 
doses should not be taken unless it is within 6 hours of the scheduled dosing and vomited doses 
should be retaken only if the tablet is visible in the vomitus. 
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Idelalisib will be taken twice daily. Idelalisib should be taken at approximately the same times 
each day. Ideally, doses should be taken at approximately 12 hour intervals as instructed 
(eg, at 7 AM and at 7 PM). While it is realized that variations in dosing schedule may occur in 
the outpatient setting, the prescribed regimen should be followed as closely as possible.
5.2.5.
Dispensing
The clinic staff (eg, pharmacist or other qualified person) will be responsible for dispensing 
idelalisib. It is planned that idelalisib will be dispensed at 4-week intervals through the 
first 16 weeks of treatment, at 8-weeks, and at 12-week intervals thereafter. Sufficient idelalisib
will be provided for each study period at the beginning of the period. Tablets should be 
dispensed in the original bottles provided.
The clinic staff (eg, pharmacist or other qualified person) will write the subject number on each 
bottle that is dispensed. Immediately before dispensing, the clinic staff will write the bottle 
number for each dispensed bottle in the idelalisib administration record corresponding to the 
subject number.
5.2.6.
Premedication
No specific pre-medications or supporting medications are required in conjunction with idelalisib
administration.
5.2.7.
Administration Instructions
The prescribed dose of idelalisib should be taken orally. At each dose administration, the tablet 
number corresponding to the appropriate dose of idelalisib is to be swallowed whole with 
100 to 200 mL (~4 to 8 ounces) of water. In case of breakage of the tablets in the oral cavity, 
additional water should be taken as a rinse.
Idelalisib may be taken with or without food. There are no known dietary restrictions related to 
idelalisib use.
5.2.8.
Dosing Schedule
Idelalisib will be administered on a BID schedule. Idelalisib should be taken at approximately the 
same times each day.
5.2.9.
Dose Levels
Idelalisib dose levels are shown in Table 5-1. The starting dose level will be 150 mg BID. The 
lower dose level (Dose Level -1) is provided in case a subject requires a dose modification.


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Table 5-1.
Idelalisib Dose Levels
Dose Level
Dosing Regimen
Starting
150 mg BID
-1
100 mg BID
Abbreviation: BID=twice per day
Consistent with Table 5-2, if a subject experiences an AE that is suspected to be related to 
idelalisib during the course of study, idelalisib administration may be held, as necessary, until the 
AE resolves or stabilizes to an acceptable degree (as defined in Table 5-2). Thereafter, idelalisib 
may be reinitiated at either the Starting Dose Level or at Dose Level -1 consistent with the 
instructions in Section 5.2.10. A further attempt at reinitiation of therapy at Dose Level -1 may 
be attempted if the investigator feels that a second rechallenge at that dose level is medically 
appropriate. If the subject cannot tolerate idelalisib after 2 rechallenges at Dose Level -1 for the 
same AE, then the subject should be discontinued from idelalisib treatment.
After an idelalisib dose reduction, the dose need not be re-escalated, even if there is minimal or 
no toxicity with the reduced dose. However, if the subject tolerates Dose Level -1 of idelalisib
for 4 weeks, then the dose may be increased back to Starting Dose Level, at the discretion of 
the investigator. Such a re-escalation may be particularly warranted if further evaluation reveals 
that the AE that led to the dose reduction was not related to idelalisib.
5.2.10.
Idelalisib Dose Adjustments
The dose adjustment recommendations and requirements in Table 5-2 are based on the Common 
Terminology Criteria for Adverse Events (CTCAE) grade of specific toxicities. However, 
exceptions are expected for subjects who initiate study treatment with low blood counts. Clinical 
judgment should apply, and in cases of uncertainty, the study medical monitor should be 
contacted.
The dose modification instructions in Table 5-2 focus on the types of events most commonly 
associated with idelalisib. The modifications include both recommended and required actions. 
When a modification is indicated as a recommendation, it serves as a guideline; variations from 
the recommendation may be warranted based on an investigator’s individual judgment in 
considering potential risks, benefits, and therapeutic alternatives available to each subject.


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Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}
NCI CTCAE Gradea
Idelalisib
HEMATOLOGICAL ADVERSE EVENTS
Neutropenia
Grade 2 neutropenia
Recommended Action: Maintain current dose level and schedule.
Grade 3 neutropenia
Required Action: Monitor blood counts at least weekly until ANC < Grade 2.
Recommended Action: Maintain current dose level and schedule.  
Grade 4 neutropenia
(or occurrence of 
neutropenic fever or 
infection)
Required Action: 

Withhold idelalisib.  

Monitor blood counts at least weekly until ANC ≤Grade 2
Recommended Action: 

May resume idelalisib at lower dose level when ANC grade is ≤ Grade 3

Neutropenia should be managed according to established clinical guidelines.
Thrombocytopenia
Grade 3
Recommended Action: Maintain current dose level and schedule.
Grade 4
Required Action: Withhold idelalisib for bruising or bleeding until Grade 3.
Recommended Action: May resume idelalisib at initial or reduced dose level at 
investigator discretion.
NON-HEMATOLOGICAL ADVERSE EVENT
Rash
Grade 1
Recommended Action: Maintain current dose level and schedule
Grade 2
Recommended Action: Maintain current dose level and schedule 
Grade ≥3
Required Action: Withhold idelalisib until Grade 1. 
Recommended Action: Resume at lower dose level or discontinue idelalisib at 
investigator discretion.
Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)
Any Grade
Required Action: 

Discontinue idelalisib.

Institute treatment per institutional standards.

Interrupt co-administered medications potentially associated with SJS/TEN.
Bowel Perforation
Any Grade
Required Action: Discontinue idelalisib 


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NCI CTCAE Gradea
Idelalisib
Gastrointestinal Inflammation/Diarrheab
Grade 1
Required Action: 

Obtain history of onset and duration of diarrhea, including description, number 
of stools, stool composition (e.g., watery, bloody, nocturnal), travel history, 
dietary changes and a medication review to identify possible diarrheogenic 
agents.

Perform physical examination including assessment for fever, dizziness, 
abdominal pain/cramping, and weakness (e.g., evaluate for sepsis, bowel 
obstruction, dehydration).
Recommended Action: Provide anti-diarrheal agent (eg, loperamide) and maintain 
current idelalisib dose level and schedule
Grade ≥ 2 diarrhea or 
colitis (unless clinical 
diagnosis is established 
from medical history and 
physical examination)
Required Action: 

Obtain history of onset and duration of diarrhea, including description of 
number of stools and stool composition (e.g., watery, bloody, nocturnal), travel 
history, dietary changes and a medication review to identify possible 
diarrheogenic agents.

Perform physical examination including assessment for fever, dizziness, 
abdominal pain/cramping, and weakness (e.g., evaluate for sepsis, bowel 
obstruction, dehydration).

For Grade 2 colitis or diarrhea (unless clinical diagnosis is established from 
medical history and physical examination), perform stool culture for routine 
pathogens (Salmonella, Shigella, Campylobacter species, test for Clostridium 
difficile toxin, Rotavirus, Cytomegalovirus (CMV), Adenovirus), ova and 
parasites (Cryptosporidium parvum, Isospora belli, Enterocytozoon bieneusi, 
Septata intestinalis, Strongyloides, Microsporidia, Entamoeba histolytica, 
Cyclospora), and Giardia antigen. 
Recommended Action: Provide anti-diarrheal agent (eg, loperamide) and maintain 
current idelalisib dose level and schedule
Grade ≥ 3 diarrhea or 
colitis or persistent Grade 
2 diarrhea or colitis 
without clear etiology
Required Action: 

Dosing: Withhold idelalisib

Consider anti-diarrheal (eg, loperamide) and/or addition of anti-inflammatory 
agent (eg, sulfasalazine, budesonide).

Obtain history of onset and duration of diarrhea, including description, number 
of stools, stool composition (e.g., watery, bloody, nocturnal), travel history, 
dietary changes and a medication review to identify possible diarrheogenic 
agents.

Perform physical examination including assessment for fever, dizziness, 
abdominal pain/cramping, and weakness (e.g., evaluate for sepsis, bowel 
obstruction, dehydration).

For Grade 3 colitis or diarrhea (unless clinical diagnosis is established from 
medical history and physical examination), perform stool culture for routine 
pathogens (Salmonella, Shigella, Campylobacter species, testing for Clostridium 
difficile toxin, Rotavirus, Cytomegalovirus (CMV), Adenovirus), ova and 
parasites (Cryptosporidium parvum, Isospora belli, Enterocytozoon bieneusi, 
Septata intestinalis, Strongyloides, Microsporidia, Entamoeba histolytica, 
Cyclospora), and Giardia antigen.


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ld£>1alisib 
Recommended Action: 
Final 
Amendment 3 
• 
Dosing: At Grade ~1, may restune at lower dose level or discontinue idelalisib at 
investigator discretion. 
• 
Endoscopy with biopsy is strongly recommended to assess by li'ii'"'"'-----. 
immtuwhistochem.istry 
and PCR for CMV, Adenovirus PPD 
r------..1 
• 
Provide anti-dianheal agent (eg, loperamide) and maintain cm1·ent idelalisib dose 
level and schedule 
H£>patic Adv£>rs£> Ev£>nts (elevations in ALT, AST, or bilirubin) 
Gradeg 
(ALT/AST:::; 3xULN) 
(Bilirubin:::; 1.5xULN) 
Grade 2 
(ALT/AST > 3-5xULN) 
(Bilirubin > 1.5- :::; 
3xULN) 
Grade 3 
(ALT/AST>5-20xULN) 
(Bilirubin > 3-lOxULN) 
Grade 4 
(ALT/AST>20xULN) 
(Bilirubin > lOxULN) 
Recommended Action: Maintain ctUTent dose level and schedule. 
Recommended Action: Maintain ctlll'ent dose level and schedule 
Recommended Action: Monitor ALT, AST, ALP, and bilirubin at least lx per week 
tmtil all abnonnalities are Grade ::::;1; thereafter, maintain Ctlll'ent dose level. 
Recommended Action: Withhold idelalisib. 
Required Action: 
• 
Monitor ALT, AST, ALP, and bilirubin at least lx per week tmtil all 
abnonnalities are Grade :::;1. 
• 
If bilirubin abnotmality is Grade <3, restmle idelalisib at same dose level. If 
bilirubin abnonnality is Grade ;::3, resume at lower dose level. 
Required Action: 
• 
Withhold idelalisib. 
• 
Monitor ALT, AST, ALP, and bilimbin at least 1x per week tmtil all 
abnonnalities are Grade :::;1. 
• 
If bilirubin abnormality is Grade 4, discontinue idelalisib. 
Recommended Action: If bilirubin abnonnality is Grade <4, resume study dmg at 
lower dose level. 
Pneumonitis (with new onset or worsening of bas£> line dyspnea, cough, or hypoxia without obvious infec.tious 
cause) 
Grade 1 
(asymptomatic) 
Grade~2 
Required Action: Withhold idelalisib tmtilresolution to baseline. May restnne at lower 
dose level or discontinue idelalisib at investigator discretion. 
Required Action: 
• 
Discontinue idelalisib pennanently in subjects with any severity of symptomatic 
pnetunonitis and institute therapy as clinically appropriate. 
Pneumocystis jirov£>cii pn£>umonia (P JP) 
Any Grade 
Required Action: Discontinue idelalisib 
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NCI CTCAE Gradea
Idelalisib
Unequivocal CMV infectionc
Any Grade
Required Action: 

Interrupt idelalisib upon unequivocal clinical or laboratory evidence of CMV 
infection.

Treat according to established clinical guidelines.

If the benefits of resuming idelalisib are judged to outweigh the risks, 
consideration should be given to administering pre-emptive CMV therapy.
Other Nonhematological Adverse Events
Grade 2
Recommended Action: Maintain current dose level and schedule
Grade 3
Recommended Action: Withhold idelalisib until Grade 1. May resume idelalisib at 
initial or lower dose level or discontinueidelalisib at investigator discretion.
a
CTCAE, Version 4.03.
b
See section 6.2. and 7.3.2. for additional requirements regarding an AE of diarrhea
c
CMV should be diagnosed using clinical or laboratory criteria per established institutional standard
Abbreviations: ALP=alkaline phosphatase, ALT=alanine aminotransferase, ANC=absolute neutrophil count, 
AST=aspartate aminotransferase, CTCAE=Common Terminology Criteria for Adverse Events, CMV=cytomegalovirus,
G-CSF=granulocyte-colony-stimulating factor, NCI=National Cancer Institute, ULN=upper limit of normal
5.3.
Prior and Concomitant Medications
If considered necessary for the subject’s well-being, drugs for concomitant medical conditions or 
for symptom management may be given at the discretion of the investigator.
Any concomitant medications prescribed as a therapeutic intervention for or resulting in an AE 
or SAE during the course of the study and the reason for use should be recorded on the eCRFs.
5.3.1.
Anticancer or Experimental Therapies Other than Investigational 
Treatments
Except for corticosteroids, no other anticancer therapies (including chemotherapy, radiation, 
antibody therapy, immunotherapy, or other experimental therapies) of any kind are permitted. 
Subjects are not allowed to participate concurrently in any other therapeutic clinical study.
5.3.2.
Antibiotics/ PJP Prophylaxis
5.3.2.1.
Infectious Events
Patients with lymphoid cancers receiving idelalisib have developed serious and fatal infections 
during therapy. Opportunistic infections, most notably Pneumocystis jirovecii pneumonia (PJP) 
and CMV infection, have most frequently occurred within the first 6 months of treatment with 
idelalisib and are increased in the context of concurrent myelosuppressive therapy such as 
bendamustine.


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Subjects must receive trimethoprim-sulfamethoxazole or other established prophylaxis for PJP
throughout the course of idelalisib treatment, and for 2 to 6 months following the last dose of
idelalisib.  Prophylaxis must continue until the CD4+ T-cell count is documented to be 
>200 cells/mcL after idelalisib treatment ends. Subjects must permanently discontinue idelalisib 
upon diagnosis of PJP.
CMV surveillance for active disease (quantitative PCR or PP65 antigen) must be conducted 
approximately every 4 weeks throughout the course of idelalisib treatment. CMV viral load 
testing should be performed from the same specimen type whenever possible and caution should 
be exercised when comparing CMV viral load results across different testing centers. If 
unequivocal clinical or laboratory evidence of CMV infection is present, the subject must 
interrupt idelalisib treatment and undergo effective antiviral treatment according to established 
clinical guidelines. If the benefits of resuming idelalisib are judged to outweigh the risks, 
consideration should be given to administering pre-emptive CMV therapy.
In high-risk subjects (history of recurrent infection, allogeneic transplant, treatment with 
alemtuzumab, hypogammaglobulinemia) other infection prophylaxis should be considered per 
consensus guidelines. Administration of intravenous immunoglobulin is permitted per standard 
institutional practice {Raanani et al 2009}. For subjects who develop an infection, appropriate 
medical therapy should be instituted in a timely manner.
Trimethoprim sulfamethoxazole is rated a Pregnancy category C agent.  In rats, oral doses of 
533 mg/kg or 200 mg/kg produced teratologic effects manifested mainly as cleft palates.
One survey found no congenital abnormalities in 35 children whose mothers had received oral
sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter. Because 
sulfamethoxazole and trimethoprim may interfere with folic acid metabolism it should be used 
during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Dapsone is rated a Pregnancy Category C agent.  Extensive, but uncontrolled experience and 
two published surveys on the use of Dapsone in pregnant women have not shown that Dapsone 
increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can 
affect reproduction capacity. Because of the lack of animal studies or controlled human 
experience, Dapsone should be given to a pregnant woman only if clearly needed. Dapsone is 
excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates. 
Because of the potential for tumorgenicity shown for Dapsone in animal studies a decision 
should be made whether to discontinue nursing or discontinue the drug taking into account the 
importance of drug to the mother.
Atovaquone is rated a Pregnancy Category C agent.  Atovaquone is teratogenic and did not cause 
reproductive toxicity in rats at plasma concentrations up to 2 to 3 times the estimated human 
exposure. Atovaquone can cause maternal toxicity in rabbits at plasma concentrations that were 
approximately one half the estimated human exposure. Mean fetal body lengths and weights 
were decreased and there were higher numbers of early resorption and post-implantation loss per 
dam. It is not clear whether these effects are caused by atovaquone directly or are secondary to 
maternal toxicity. Concentrations of atovaquone in rabbit fetuses averaged 30% of the concurrent 


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maternal plasma concentrations. There are no adequate and well-controlled studies in pregnant 
women. Atovaquone should be used during pregnancy only if the potential benefit justifies the 
potential risk to the fetus. It is not known whether atovaquone is excreted into human milk. 
Because many drugs are excreted into human milk, caution should be exercised when 
Atovaquone is administered to a nursing woman. In a rat study, atovaquone concentrations in the 
milk were 30% ofthe concurrent atovaquone concentrations in the maternal plasma. 
Aerosolized Pentamidine (NebuPent) is a Pregnancy Category C agent. There are no adequate 
and well controlled studies ofNebuPent in pregnant women. One literature report indicated that 
intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; 
teratogenicity was not observed in this study. It is unknown whether pentamidine administered 
via the aerosolized route crosses the placenta at clinically significant concentrations. It is not 
known whether NebuPent can cause fetal harm when administered to a pregnant woman. 
NebuPent should be given to a pregnant woman only if clearly needed. It is not known whether 
NebuPent is excreted in human milk. NebuPent should not be given to a nursing mother unless 
the potential benefits are judged to outweigh the unknown risks. 
5.3.3. 
Antidiarrheals 
As needed, subjects may be prescribed loperamide (Imodium® or others) or diphenoxylate and 
atropine (Lomotil®) to control diarrheal symptoms. 
5.3.4. 
Corticosteroids 
Subjects may receive topical, inhaled, enteric, or systemic corticosteroids while on study. 
5.3.5. 
Granulocyte Colony-Stimulating Factors and Erythropoietin 
Granulocyte-macrophage colony-stimulating factor (GM-CSF) should not be administered given 
the potential for GM-CSF-related inflammatory symptoms. 
G-CSF (filgrastim, PEG-filgrastim, lenograstim) may be administered in response to 
Grade 4 neutropenia or neutropenic complications; (see Table 5-2). 
While erythropoietic agents (eg, erythropoietin or darbepoetin) may be administered for 
Grade ~3 anemia, their use in this study is discouraged given the potential to confound 
assessments of improvements in bone marrow function related to idelalisib. 
5.3.6. 
Drugs that Alter CYP3A-Dependent Metabolism 
Idelalisib is metabolized to its major metabolitdPPD 
via aldehyde oxidase and 
cytochrome P450 3A (CYP3A). Idelalisib also undergoes minor metabolism by UDP 
glucoronosyltransferase 1-4 (UGT1A4). The AUC of idelalisib was increased 1.8 fold when 
idelalisib was co administered with a strong CYP3A inhibitor. Therefore, if subjects are taking 
concomitant strong CYP3A inhibitors, the subject should be monitored closely for signs of 
idelalisib toxicity and the dose modifications for adverse reactions should be followed in the 
event of toxicity (see Table 5-2). 
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Additionally, idelalisib exposures are approximately 75% lower when coadministered with 
rifampin, a highly potent inducer of CYP3A. Therefore, avoid coadministration of strong 
inducers ofCYP3A (rifampin, carbamazepine, phenytoin, and St. John's wort) with idelalisib. 
5.3.7. 
Drugs that undergo CYP3A-Dependent Metabolism 
The major metabolite of idelalisib;PPD 
, is a reversible and time dependent inhibitor of 
CYP3A; accordingly, coadministration of idelalisib with midazolam, a probe CYP3A substrate, 
resulted in a ~5-fold increase in midazolam systemic exposure (AUC). Coadministration of 
drugs that are narrow therapeutic index CYP3A substrates with idelalisib may result in an 
increase in their systemic exposures (eg, antiarrhythmics, calcium channel blockers, 
benzodiazepines, certain HMG-CoA reductase inhibitors, phosphodiesterase-S [PDE5] 
inhibitors, warfarin). Avoid coadministration of drugs that are narrow therapeutic index CYP3A 
substrates ( eg, alfentanil, cyclosporine, sirolimus, tacrolimus, cisapride, pimozide, fentanyl, 
quinidine, ergotamine, dihydroergotamine, astemizole, terfenadine) with idelalisib. 
5.3.8. 
Immunization 
Because of its actions to inhibit PI3Ko-dependent B-cell function, high doses of idelalisib can 
impair primary or secondary responses to immunization in animals. 
The specific clinical relevance ofthese findings with idelalisib is unknown. However, for 
subjects who are at substantial risk of an infection ( eg, influenza) that might be prevented by 
immunization, consideration should be given to providing the vaccine prior to initiation of study 
therapy. 
Of note, the safety of immunization with live viral vaccines following idelalisib therapy has not 
been studied and vaccination with live virus vaccines during study treatment is not 
recommended. 
5.3.9. 
Ultraviolet Exposure 
While nonclinical findings suggest the hypothetical potential for phototoxicity in humans, 
available clinical data do not reveal a photosafety concern. Although specific clinical correlates 
for these non clinical data are not available, investigators and study subjects should be observant 
for the possibility that study participants may have exaggerated sunburn reactions ( eg, burning, 
erythema, exudation, vesicles, blistering, edema) involving areas of skin exposed to ultraviolet 
light. 
5.3.10. 
Surgery 
There are no known effects of idelalisib on coagulation or wound healing. Pending receipt of 
additional information and considering the subject's current platelet counts, idelalisib may be 
continued in the peri-procedural period in subjects who require surgery or invasive procedures. 
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5.4.
Accountability for Idelalisib
The disposition of all idelalisib should be documented from the time of receipt at the site through 
subject dispensing and return.
Study personnel must ensure that idelalisib is kept in a secure locked area with access limited to 
authorized personnel. The idelalisib must not be used outside the context of this protocol. Under 
no circumstances should the investigator or site personnel supply idelalisib to other investigators 
or clinics, or allow the idelalisib to be used other than as directed by this protocol.
The investigator and/or the responsible site personnel must maintain accurate records of the 
receipt of idelalisib shipped by Gilead Sciences or its designee, including, but not limited to, the 
date received, lot number, amount received, and the disposition of all idelalisib. Upon receipt of 
a drug shipment, the shipment must be logged into the idelalisib accountability records, these 
records must also be maintained to include the subject number to whom the idelalisib was 
dispensed and the date, quantity and lot number of the idelalisib dispensed.
Depending upon the decision of Gilead Sciences, remaining unused idelalisib supply will be 
returned to Gilead Sciences or its designee after the study is completed or will be discarded or 
destroyed at the clinical site. If the idelalisib is discarded or destroyed at the clinical site, 
standard institutional policy should be followed. Records documenting the date of idelalisib
shipping or destruction, relevant lot numbers, and amount shipped or destroyed should be 
maintained.
5.4.1.
Overdose Precautions
In Phase 1 studies, an MTD for idelalisib was not reached when administering the drug 
continuously at dose levels of 350 mg/dose BID (700 mg per day) {Coutre et al 2011, Kahl et al 
2011}. However, in this protocol, an overdose is defined as administration of more than the 
prescribed daily dose (ie, >300 mg in a single day).
The Gilead Sciences medical monitor should be contacted if an idelalisib overdose occurs. Cases 
of idelalisib overdose will result in specific reporting requirements.
5.4.2.
Inadvertent Exposure and Spill Precautions
Based on available data from nonclinical studies, idelalisib does not appear to be acutely toxic, 
genotoxic, or irritative at levels that are likely to result from inadvertent exposure to the contents 
of broken tablets. However, personnel handling the drug should use reasonable precautions to 
avoid eye contact, skin contact, inhalation, or ingestion of the idelalisib product. For further 
information regarding inadvertent exposure and spill precautions, please consult the idelalisib
investigator brochure.


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5.4.3.
Investigational Medicinal Product Return or Disposal
Subjects will be instructed to return any unused idelalisib in the original container at post 
treatment study visits. Returned medication will be reconciled by the investigator in order to 
monitor the subject’s compliance with the medication regimen. When possible, all idelalisib
returned by the subject should be retained for review by the study site monitor prior to return to 
Gilead Sciences or destruction.
5.5.
Discontinuation from Study
Subject study participation may be ended due to any of the follow reasons:

Withdrawal of consent

Objective evidence of disease progression.

Unacceptable toxicity or unable to tolerate a second rechallenge for the same AE.

Any subject who becomes pregnant or begins breastfeeding.

Initiation of non-protocol specfied anticancer therapy.

Noncompliance with idelalisib administration, study procedures, or study requirements.

The investigator may discontinue idelalisib, if it is not in the subject’s best interest to 
continue.

Any subject who is lost to follow-up.

Death

Discontinuation of study by the Sponsor, a regulatory agency, or an EC

Any subject who is diagnosed with any grade SJS or TEN, Grade ≥2 pneumonitis, or any 
grade PJP.

Any subject whose benefit-risk profile is not deemed positive by the investigator should 
discontinue study drug.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Table 6-1 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment 
6.1.1.
Subject Recruitment
This study will enroll subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure who have had objective evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC and no toxicities prior to enrollment in this study that would
preclude initiating therapy with idelalisib. The study sponsor will post a description of the study 
on the ClinicalTrials.gov website.
6.1.2.
Subject Compensation for Participation
Subjects will not be paid for participation in the study other than medical care that may be 
provided. Payments for such items as lost wages, disability, discomfort due to injury, or meals 
obtained while waiting at the clinical research center will not be provided. Through the informed 
consent process, study candidates will be notified that their insurance company could be charged 
for standard care that is a component of this research study and that subjects may be responsible 
for co-payments and deductible payments that are typical for their insurance coverage.
6.1.3.
Screening Visit
The investigator must inform each prospective subject of the nature of the study, explain the 
potential risks, and obtain written informed consent from the subject and/or a legal guardian 
prior to performing any study-related screening procedures. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (CRF/eCRF).  
All other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history CRF/eCRF.  
See Section 7 Adverse Events and Toxicity Management for additional details.
6.2.
Treatment Assessments
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all SAEs, as well as any non-serious all grade AEs on the AE case 
report form (eCRF). All other untoward medical occurrences observed during the screening 


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period, including exacerbation or changes in pre-existing conditions are considered medical 
history (not collected for this study). See Adverse Events and Toxicity Management (Section 7) 
for additional details.
While on study, the subject will return at regular intervals for the following procedures:

Evaluation of disease status per standard of care

Laboratory lab tests as outlined under section 6.2.2. 

Recording of all grade AEs and all SAEs
For an AE of Diarrhea or Colitis:
1. Obtain history of onset and duration of diarrhea, including description of number of 
stools and stool composition (eg, watery, bloody, nocturnal), travel history, dietary 
changes and a medication review to identify possible diarrheogenic agents
2. Perform physical examination including assessment for fever, dizziness, abdominal 
pain/cramping, and weakness (ie, evaluate for sepsis, bowel obstruction, dehydration)

Return of used drug supplies and dispensing of new idelalisib supply
The specific study procedures to be conducted for each subject enrolled in the study are 
presented in Table 7-1 and are described in the sections that follow.
6.2.1.
Clinical Evaluation
While on study, the subject will be followed for disease status according to standard of care. At 
each study visit the subject’s disease status will be assessed. If no change in disease status is 
identified and the subject is dispensed additional idelalisib, the most recent prior response 
documented for the study will be recorded.
6.2.2.
Laboratory Assessments
Blood samples for ALT, AST, total bilirubin will be collected at Screening, Day 1, Weeks 4, 8, 
12, 16, 168, every 12 weeks thereafter, and the End of Study (EOS) Visit.
Blood samples for CMV will be collected at Screening and every 4 weeks thereafter throughout 
study participation.
Blood samples for ANC will be collected at Screening and every 2 weeks through Week 24.
Blood samples for Pneumococcal, Haemophilus Influenzae Type B (Hib), and Tetanus titers will 
be taken at screening


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Blood samples for immune-monitoring will be collected at Screening, Weeks 4, 12 and every 
12 weeks thereafter, and the EOS Visit: 
• 
Lymphocyte subset panel using flow cytometry (immunophenotyping) 
• 
Quantitative immunoglobulins: IgG, IgM, IgA 
• 
Serum CH50 level 
6.2.2.1. 
Evaluation for Gastrointestinal Events/Colitis 
For Grade 2 colitis and diarrhea (unless clinical diagnosis is established from medical history and 
physical examination), the following testing is required: 
• 
Stool culture for routine pathogens (Salmonella, Shigella, Campylobacter species, 
Clostridium diffi.cile toxin, Rotavirus, Cytomegalovirus, Adenovirus) 
• 
Stool for Ova and Parasites (Cryptosporidium parvum, Isospora belli, Enterocytozoon 
bieneusi, Septata intestinalis, Strongyloides, Microsporidia, Entamoeba histolytica, 
Cyclospora), Giardia antigen 
For Grade 2' 3 or persistent Grade 2 colitis or diarrhea without clear etiology (eg, clostridium 
diffi.cile enterocolitis), endoscopy with biopsy is strongly recommended. All biopsy samples 
should include immunohistochemistry (IHC) and PCR for CMV, Adenovirus. 
PD 
6.2.2.2. 
Differentiation Between Small-bowel and Large-bowel Diarrhea 
Differentiation between small-bowel and large-bowel diarrhea on a clinical basis if 
recommended. If unclear, consider upper and lower tract endoscopy with biopsy. 
• 
Small bowel diarrhea is characterized by large volume diarrhea (more than one per day), 
possibly associated dehydration weight loss and paraumbilical pain. Consider an endoscopic 
small-bowel biopsy and evaluate other etiologies such as celiac disease. 
• 
Large-bowel diarrhea may present with lower pelvic pain, tenesmus, generally smaller stool 
volumes with gross blood frequently found in the stool. Consider a colonoscopic evaluation 
and biopsy. 
6.3. 
End of Study 
Subjects will be withdrawn from this study if they develop progressive disease, unacceptable 
toxicity related to idelalisib, withdraw consent, are noncompliant, or are lost to follow up or die. 
In this event, the following procedures should be performed: 
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
Return of used and unused drug supply

Recording of all Grade AEs and all SAEs

Investigator Response Assessment

Laboratory assessments as outlined in Table 6-1

Recording of the reason for withdrawal

Deaths occurring within 30 days following the last dose of idelalisib, even if occurring after 
the End of Study Visit, will be captured.


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Table 6-1.
Schedule of Study Procedures
Period
Screen
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15+
End of 
study
Week
-4
0
2
4
6
8
10
12
14
16
18
20
22
24
Q4 
weeks
Q12 
weeks
Study Day
Within
-28 days
1
14
28
42
52
70
84
98
112
126
140
154
168
Visit Window
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±7
±7
Informed consent
X
Serum -HCGa
X
Pneumococcal, Hib, Tetanus titers
X
ALT/AST/total bilirubin
X
X
X
X
X
X
X
X
X
Urine pregnancy testa
X
X
X
X
X
X
X
X
ANCb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CMV surveillance
X
X
X
X
X
X
X
Xc
Immune Monitoring
X
X
X
X
X
X
Assess adverse events and SAEsd
X
X
X
X
X
X
X
X
Record concomitant 
medicationse
X
X
X
X
X
X
X
X
Idelalisib dispensing/accounting
X
X
X
X
X
X
X
X
Investigator response 
assessmentf
X
X
X
X
X
X
X
X
Abbreviations: -HCG=beta human chorionic gonadotropin, ALT=alanine aminotransferase, AST=aspartate aminotransferase, Hib = Haemophilus Influenzae Type B
a
For women of child bearing potential; Serum -HCGto be collected to be collected at screening, urine pregnancy test to be collected at visits from first dose of idelalisib to EOS
b
Absolute neutrophil count (ANC) will be monitored at least every two weeks for the first 24 weeks of idelalisib treatment
c
CMV surveillance must be conducted approximately every 4 weeks throughout the course of idelalisib treatment
d
For an AE of Diarrhea/Colitis: 1) Obtain history of onset and duration of diarrhea, including description of number of stools and stool composition, travel history, dietary 
changes and a medication review to identify possible diarrheogenic agents and 2) Perform physical examination including assessment for fever, dizziness, abdominal 
pain/cramping, and weakness
e
Concomitant medications only collected if it is related to an AE
f
Record investigator response assessment if obtained per standard of care


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Lymphocytosis

Laboratory abnormalities not requiring clinical intervention or further investigation. Such 
abnormalities will be captured as part of overall laboratory monitoring.

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
CRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)


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
In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to idelalisib interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Idelalisib and Procedures
The investigator or qualified sub-investigator is responsible for assessing the relationship to 
idelalisib therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than idelalisib. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.


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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg., venipuncture)
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the CTCAE, Version 4.03 and available at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or 
Grade 5 (fatal) to describe the maximum intensity of the adverse event. For purposes of 
consistency with the CTCAE, these intensity grades are defined in Table 7-1.
Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Sign or symptom is present, but it is easily tolerated, is not expected to have a 
clinically significant effect on the subject’s overall health and well-being, does 
not interfere with the subject’s usual function, and is not likely to require 
medical attention.
Grade 2
Moderate
Sign or symptom causes interference with usual activity or affect clinical status, 
and may require medical intervention.
Grade 3
Severe
Sign or symptom is incapacitating or significantly affects clinical status and 
likely requires medical intervention and/or close follow-up.
Grade 4
Life-threatening
Sign or symptom results in a potential threat to life.
Grade 5
Fatal
Sign or symptom results in death.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events listed in Section 7.1.2.


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7.3.
Evaluation, Intervention, and Drug Discontinuation for Specific Adverse 
Events or Conditions
7.3.1.
Dermatological Events (Idelalisib)
Subjects receiving idelalisib with ≥Grade 3 rash have generally presented with a maculopapular 
rash on the trunk and extremities that is occasionally associated with fever and/or pruritus and 
responded to treatment with diphenhydramine and/or topical or oral corticosteroids. 
For subjects who develop Grade ≥3 rash for which an underlying etiology cannot be identified 
(e.g., infection, co-suspect drug), study drug must be interrupted. Severe cutaneous reactions, 
including fatal events of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), 
have been reported in subjects receiving idelalisb. Assessment of potential causal association 
between idelalisib and the occurrence of SJS or TEN has been confounded by the 
coadministration of antineoplastic agents (e.g., bendamustine, rituximab) and/or other 
concomitant medications known to be associated with SJS or TEN (e.g., allopurinol). If SJS or 
TEN is suspected, idelalisib and all coadministered medications associated with SJS or TEN 
should be interrupted and the subject treated accordingly. 
Subjects should be monitored for the development of SJS, TEN, or other severe cutaneous 
reactions and idelalisib treatment should be discontinued if such events occur.
7.3.2.
Gastrointestinal Events
Isolated cases of gastrointestinal inflammation (eg, stomatitis, colitis, cecitis) have been noted in 
subjects receiving idelalisib. Rare cases of gastrointestinal perforation have occurred, generally 
in the setting of occult carcinoma, mesenteric embolus or diverticular disease.  Study treatment 
(idelalisib/placebo) must be discontinued in subjects who experience bowel perforation
Cholangitis manifest as hyperbilirubinemia out of proportion to serum transaminase elevations 
has been observed. While disease-related factors, neutropenia, toxicity from prior therapies, 
effects of ongoing supportive care, or pre-existing cholelithiasis may have initiated such events, 
it is possible that idelalisib played a contributory role. In such subjects, rechallenge with 
idelalisib has been possible and has not been associated with other severe adverse events. 
Subjects who have developed evidence of enteritis during idelalisib therapy have been 
successfully treated with antidiarrheals (eg, loperamide) and with enteric steroidal (eg, 
budesonide) or non-steroidal (eg sulfasalazine [Azulfidine®]) anti-inflammatory agents and have 
been able to continue or resume idelalisib.
For study subjects who develop severe abdominal pain the possibility of a bowel obstruction or 
perforation should be considered. Appropriate clinical and radiographic examination should be 
performed and supportive care or surgical intervention should be considered. Upon recovery, 
rituximab may be resumed.


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7.3.2.1.
Investigation for Idelalisib Late Onset or Severe Diarrhea/Colitis
See CTCAE Version 4.03 for definitions of colitis and diarrhea.
Among idelalisib-treated patients who reported diarrhea or colitis, the median time to onset of 
any grade diarrhea or colitis was 1.9 months (range, 0.0–29.8), of grade 1 or 2 was 1.5 months 
(range, 0.0–15.2) and of grade 3 or 4 was 7.1 months (range, 0.5–29.8). Kaplan–Meier curves of 
time to onset of diarrhea or colitis are shown for all idelalisib- treated patients in Figure 7-1
{Coutre et al 2015}.
Figure 7-1.
Kaplan-Meier Time to Diarrhea or Colitis
Idelalisib-associated severe diarrhea responds poorly to antimotility agents however, median 
time to resolution ranged between 1 week and 1 month across trials following interruption of 
idelalisib treatment and, in some instances, initiation of corticosteroid treatment
{Gilead Sciences Inc 2014}.
7.3.3.
Hepatic Events
Transaminase Elevations: Consistent with observations in a dog toxicology study, reversible 
asymptomatic ALT/AST increases were also observed early in the idelalisib program in phase 1 
studies (101-02 and 101-07) in subjects with hematologic malignancies. Transaminase elevations 
generally occurred within 4 to 12 weeks of drug initiation, and resolved spontaneously over a 
period of 2 to 4 weeks with drug being continued for Grade 1 and 2 elevations and drug withheld 
for Grade 3 or 4 elevations until resolution. These early observations have been consistent with 
the ongoing experience with idelalisib treatment and transaminase elevations are now well 
characterized as most frequently asymptomatic, transient and occurring within the first 3 months 
of treatment.


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Grade 1 or 2 elevations commonly resolve despite continued idelalisib treatment and Grade 3 or 
4 elevations can be managed by withholding idelalisib. Successful rechallenge after resolution at 
either the same or lower dose level of idelalisib has been achieved in the majority of subjects. 
There has been no evidence of impaired synthetic function. Close monitoring of hepatic 
laboratory tests during therapy is important to allow for appropriate idelalisib interruption and 
reinstitution so that subjects may continue with study drug treatment.
7.3.4.
Hematological and Immunological Events
In the Phase 1 experience with idelalisib in patients with NHL and CLL, subjects with Grade 3 
neutropenia, anemia, and/or thrombocytopenia were enrolled to clinical trials. Decreased levels 
of neutrophil counts, hemoglobin, or platelet counts during idelalisib administration were largely 
due to minor fluctuations in these parameters among subjects with pre-existing hematological 
abnormalities due to disease or prior therapy. Thus, idelalisib did not appear to induce overt 
myelosuppression. Obvious patterns of drug-mediated reductions in circulating CD4+ 
lymphocyte counts or suppression of serum IgG levels were also not observed.
Treatment-emergent Grade 3 or 4 neutropenia events, including febrile neutropenia, have occurred in 
subjects treated with idelalisib. All subjects should have their blood counts monitored at least every 
2 weeks for the first 6 months of idelalisib treatment. For subjects who develop Grade 3 neutropenia, 
blood counts must be monitored at least weekly. For subjects who develop Grade 4 neutropenia, 
idelalisib must be interrupted and blood counts monitored at least weekly until ANC is ≥ 0.5 Gi/L, at 
which point, idelalisib may be resumed at a lower dose level.  Neutropenia should be managed 
according to established clinical guidelines.
No modification of any drug for changes in circulating CD4+ counts or Ig levels is planned.
7.3.5.
Pulmonary Events
Documented bacterial, fungal, viral, and pneumocystis pneumonias have been observed in 
patients receiving idelalisib, primarily in patients with CLL. Some study subjects receiving 
idelalisib alone or in combination have developed evidence of pneumonitis without documented 
pulmonary infection. 
Given the potential for infectious or drug-related pulmonary adverse events, clinicians should be 
particularly observant for evidence of respiratory events in subjects participating in this trial. 
Subjects who describe pulmonary symptoms (eg, dyspnea on exertion, cough, 
shortness of breath); manifest a decline from baseline of 5% in oxygen saturation, or 
demonstrate evidence of pulmonary inflammation (eg, focal or diffuse interstitial pattern or 
ground-glass opacities on chest CT) should be evaluated. Potential bacterial, fungal, or viral 
etiologies should be assessed. Noninfectious etiologies such as pulmonary edema or 
thromboembolism should also be considered.
As appropriate for the clinical situation and culture results, subjects should be treated empirically 
or given specific antibiotics, antifungals, or antiviral agents for a cultured organism. Supportive 
care, including oxygen or mechanical ventilation, should be provided as necessary.


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For subjects with suspected Grade 1 pneumonitis (asymptomatic), withhold idelalisib until 
resolution to baseline. Upon resolution to baseline, idelalisib may be resumed at lower dose level 
or discontinued at investigator discretion. For subjects with suspected Grade ≥2 pneumonitis (eg, 
new onset or worsening of baseline cough, dyspnea, hypoxia and/or a diffuse interstitial pattern 
or ground-glass opacities on chest imaging without obvious infectious etiology), idelalisib must 
be discontinued permanently and therapy initiated as clinically appropriate.
7.3.6.
Secondary Malignancies
Subjects receiving idelalisib for CLL or iNHL have developed pre-malignant and secondary 
malignant diseases, such as basal cell carcinoma, myelodysplastic syndrome, myeloproliferative 
disorders, and more aggressive lymphoid malignancies (eg, have had Richter transformation). 
Generally this has occurred in subjects who have received multiple previous lines of therapy and 
when idelalisib is combined with other therapies such as rituximab or bendamustine. The specific 
association of the therapeutic agents with these types of events has not been determined.
There are reports of pre-malignant and malignant diseases that have developed in subjects who 
have been treated with bendamustine, including myelodysplastic syndrome, myeloproliferative 
disorders, acute myeloid leukemia, and bronchial carcinoma. The specific association of the 
therapeutic agents with these types of events has not been determined.
7.3.7.
Tumor Lysis Syndrome
Tumor lysis syndrome has not been observed with idelalisib monotherapy. 
When idelalisib is combined with other agents known to induce tumor lysis syndrome, 
prophylaxis with agents such as allopurinol may be considered. The benefit versus risk of 
prophylactic agents must be carefully considered given a potential of increased risk of severe 
skin toxicity.
Subjects with tumor lysis syndrome should receive rapid reversal of hyperkalemia, intravenous 
hydration, antihyperuricemic agents, and appropriate cardiac and renal support, including 
dialysis as indicated. Upon recovery to baseline functioning, such subjects should continue study 
treatment including study drug (idelalisib/placebo).
7.4.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
All SAEs, regardless of cause or relationship, that occur after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) or designee as instructed. 
This also includes any SAEs resulting from protocol-associated procedures performed from 
screening onwards.


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All AEs, regardless of cause or relationship, that occur from initiation of study medication until 
30 days after last administration of idelalisib must be reported to the eCRF database as 
instructed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of idelalisib, regardless of causality, should also be reported.
All AEs should be followed up until resolution if possible. If by the last day on study (including 
the off-study medication follow-up period) the AE has not resolved, then the AE will be 
followed up until the investigator and/or Gilead Sciences determine that the subject's condition is 
stable. However, Gilead Sciences may request that certain AEs be followed until resolution.
Investigators are not obligated to actively seek SAEs after the 30 day period. However, if the 
investigator learns of any SAEs that occur after study participation has concluded and the event 
is deemed relevant to the use of idelalisib, he/she should promptly document and report the event 
to Gilead DSPH or designee as instructed.
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guidelines.
7.4.1.
Serious Adverse Event (eSAE) Reporting Process 
Site personnel record the SAE on the paper serious adverse event reporting form and submit via 
fax to Gilead DSPH within 24 hours.
All AEs and SAEs will be recorded in the CRF/eCRF database within the timelines outlined in 
the CRF/eCRF completion guideline.
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
Additional information may be requested to ensure the timely completion of accurate safety 
reports.
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/eCRF and the event description section of the SAE 
form.
7.5.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.


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Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with idelalisib. The investigator should notify the IEC of SUSAR reports as soon as is practical, 
where this is required by local regulatory agencies, and in accordance with the local institutional 
policy. 
7.5.1.
Reporting of Adverse Events Relating and Other Anticipated Medical Events 
in the Study Population
Given the endpoints of the study and in order to maintain the integrity of the study, the following 
events that are assessed as unrelated to idelalisib will not be considered SAEs:

Progression of lymphoid malignancy

Death related to progression of lymphoid malignancy

Disease progression and death from disease progression should be reported as SAEs by the 
investigator only if it is assessed that the idelalisib caused or contributed to the disease 
progression (ie, by a means other than lack of effect).  Unrelated disease progression should 
be captured on the eCRF.
These will be reported, as appropriate, in the final clinical study report and in any relevant 
aggregate safety reports.
7.5.2.
Toxicity Management 
See Table 5-2 for more information related to recommended dose modifications associated with 
toxicities. Please refer to the current idelalisib IB for information related to toxicity management.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.


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An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study to the Gilead DSPH using the pregnancy 
report form within 24 hours of becoming aware of the pregnancy.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post 
study must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH  using the pregnancy outcome 
report form. If the end of the pregnancy occurs after the study has been completed, the outcome 
should be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: 
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477. 
Pregnancies of female partners of male study subjects exposed to idelalisib must also be reported 
and relevant information should be submitted to Gilead DSPH using the pregnancy and 
pregnancy outcome forms within 24 hours. Monitoring of the subject should continue until the 
conclusion of the pregnancy. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead DSPH, fax number +1 650 522-5477
or email Safety_FC@gilead.com. 
Refer to Appendix 2 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.


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7.6.2.2.
Reporting Other Special Situations
All other special situation reports (excluding pregnancy) must be reported on the special 
situations report form and forwarded to Gilead DSPH within 24 hours of the investigator 
becoming aware of the situation. These reports must consist of situations that involve idelalisib, 
but do not apply to concomitant medications. Except for situations that result in AEs, special 
situations involving concomitant medication will not be reported. Any inappropriate use of 
concomitant medications prohibited by this protocol should not be reported as “misuse,” but may 
be more appropriately documented as a protocol deviation.
Refer to the CRF/eCRF completion guidelines for full instructions on the mechanism of special 
situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE CRF/eCRF and/or the SAE report form. Details of the symptoms 
and signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives
As noted in Section 2, the primary objective is to provide idelalisib to subjects receiving
GS-9820 in Study GS-US-315-0102 at the time of study closure who have had objective 
evidence of clinical benefit defined as at least stable disease on imaging assessed by the IRC and 
no toxicities prior to enrollment in this study that would preclude initiating therapy with 
idelalisib.
8.2.
Safety Endpoints
Safety will be assessed with endpoints including incidence of ≥Grade 3 AEs, SAEs, and deaths.
8.3.
Analysis Sets
Both safety and efficacy will be assessed using data collected from subjects who received at least 
1 dose of idelalisib.
8.4.
Analysis Methods
All the analyses will be limited to descriptive summaries and listings. Categorical variables will 
be summarized with the number and percentage of subjects in each category. Continuous 
variables will be summarized by presenting n, mean, standard deviation, median, Q1, Q3, 
minimum and maximum.
8.5.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable sub-investigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any sub-investigator’s) participation in the study. The investigator and 
sub-investigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Independent Ethics Committee (IEC) Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IEC. The investigator will not begin any study subject activities until 
approval from the IEC has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IEC any modifications made to the protocol or any accompanying material to be provided to 
the subject after initial IEC approval, with the exception of those necessary to reduce immediate 
risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IEC-approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately signed 


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and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IEC or local 
requirements. 
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form submitted to the Sponsor. NOTE: The investigator must keep a screening log showing 
codes, names, and addresses for all subjects screened and for all subjects enrolled in the trial.
Subject data will be processed in accordance with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, CRF/eCRF, idelalisib, and any other study information, 
remain the sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IEC
and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Birth dates will be collected as per local regulatory requirements, as needed

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);


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
Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of idelalisib, including dates of dispensing and 
return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 
data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), the investigator will use his/her log in 
credentials to confirm that the forms have been reviewed, and that the entries accurately reflect 
the information in the source documents. The eCRF capture the data required per the protocol 


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schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (eg data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Drug Accountability and Return
Gilead recommends that used and unused idelalisib supplies be returned to the shipping facility 
from which it came for eventual destruction. The study monitor will provide instructions for 
return. If return is not possible, the study monitor will evaluate each study center’s disposal 
procedures and provide appropriate instruction for destruction of unused idelalisib supplies. If 
the site has an appropriate standard operating procedure (SOP) for drug destruction as 
determined by Gilead QA, the site may destroy used (empty or partially empty) and unused 
idelalisib supplies in accordance with that site’s approved SOP. A copy of the site’s approved 
SOP will be obtained for central files. 
If idelalisib is destroyed on site, the investigator must maintain accurate records for all idelalisib
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the idelalisib. Upon study completion, copies of 
the idelalisib accountability records must be filed at the site. Another copy will be returned to 
Gilead.
The study monitor will review idelalisib supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to appropriately qualified personnel from Gilead Sciences or 
its representatives, to IECs, or to regulatory authority or health authority inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IEC in 
accordance with local requirements and receive documented IEC approval before modifications 
can be implemented.


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9.2.2.
Communications with Regulatory Authorities
Gilead Sciences, working either directly or through designees, will assume responsibility for 
regulatory interactions with relevant regulatory authorities. Gilead Sciences will maintain an 
IND for idelalisib in support of the study in the United States and will maintain similar 
regulatory applications with other regulatory authorities, as required for conduct of the study. In 
fulfilling this responsibility, Gilead Sciences (or a designee) will collect, assemble, and 
communicate all required regulatory documents (eg, Form FDA 1572, investigator financial 
disclosure forms, protocol and protocol amendments, investigator brochures, informed consent 
documents, annual reports) as required by regulation. Gilead Sciences (or a designee) will also 
assume responsibility for adverse event reporting to regulatory authorities as described in 
Section 7.5.
9.2.3.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). Gilead 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly 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.
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg attendance at Investigator's Meetings.  If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
CRF/eCRF.
The monitor is responsible for routine review of the CRF/eCRF at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the CRF/eCRF. The investigator agrees to cooperate with the monitor to 
ensure that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies) and IECs. In terminating the study, Gilead and the investigator will 
assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
Coutre S, Barrientos JC, Brown JR, De Vos S, Furman RR, Keating MJ, et al. Safety of idelalisib 
in B-cell malignancies: Integrated analysis of eight clinical trials [Presentation 
EHA-3983]. 20th Congress of European Hematology Association (EHA); 2015; 
Vienna, Austria. 
Coutre S, Byrd J, Furman R, Brown J, et al. Phase I study of CAL-101, an isoform-selective 
inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously 
treated chronic lymphocytic leukemia [Abstract]. 47th Annual Meeting of the 
American Society of Clinical Oncology (ASCO); 2011 June 3; Chicago, IL. 
Di Bella N, Taetle R, Kolibaba K, Boyd T, Raju R, Barrera D, et al. Results of a phase 2 study of 
bortezomib in patients with relapsed or refractory indolent lymphoma. Blood 
2010;115 (3):475-80.
Diehl V, Thomas RK, Re D. Part II: Hodgkin's lymphoma--diagnosis and treatment. Lancet 
Oncol 2004;5 (1):19-26.
Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia. Lancet 2008;371 (9617):1017-29.
Eichhorst B, Hallek M, Dreyling M. Chronic lymphocytic leukaemia: ESMO Clinical Practice 
Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21 Suppl 
5:v162-4.
Friedberg JW. New strategies in diffuse large B-cell lymphoma: translating findings from gene 
expression analyses into clinical practice. Clin Cancer Res 2011;17 (19):6112-7.
Gilead Sciences Inc. ZYDELIG® (idelalisib) tablets, for oral use. U.S. Prescribing Information. 
Foster City, CA. July 2014:
Gilead Sciences Limited. Zedelig (idelalisib) 150mg. Summary of Product Characteristics. 
Cambridge,United Kingdom. Revised  21 July.  2015:
Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Bortezomib in 
patients with relapsed or refractory mantle cell lymphoma: updated time-to-event 
analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 2009;20 
(3):520-5.
Gribben JG, O'Brien S. Update on therapy of chronic lymphocytic leukemia. J Clin Oncol 
2011;29 (5):544-50.


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Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of 
rituximab to fludarabine and cyclophosphamide in patients with chronic 
lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376 
(9747):1164-74.
Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, et al. Phase III study 
to evaluate temsirolimus compared with investigator's choice therapy for the 
treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27 
(23):3822-9.
Hoppe RT, Advani RH, Ambinder RF, Bierman PJ, Bloomfield CD, Blum K, et al. Hodgkin 
disease/lymphoma. J Natl Compr Canc Netw 2008;6 (6):594-622.
Jost L. Hodgkin's disease: ESMO clinical recommendations for diagnosis, treatment and follow-
up. Ann Oncol 2007;18 (Suppl 2):ii53-4.
Kahl B, Byrd J, Flinn I, Wagner-Johnston N, Spurgeon S, al E. Significant Clinical Activity Of 
Cal-101, An Isoform-Selective Inhibitor Of Phosphatidylinositol 3 Kinase P110D, 
In Patients With Relapsed Or Refractory Indolent And Mantle Cell Lymphoma 
[Abstract 350] 11th Triennial International Conference on malignant Lymphoma 
(Icml). Lugano, Swizterland: 2011:
Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, et al. Therapeutic role of alemtuzumab 
(Campath-1H) in patients who have failed fludarabine: results of a large 
international study. Blood 2002;99 (10):3554-61.
Kuruvilla J. Standard therapy of advanced Hodgkin lymphoma. Hematology / the Education 
Program of the American Society of Hematology. American Society of 
Hematology 2009:497-506.
Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B, et al. Immunochemotherapy 
with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone 
significantly improves response and time to treatment failure, but not long-term 
outcome in patients with previously untreated mantle cell lymphoma: results of a 
prospective randomized trial of the German Low Grade Lymphoma Study Group 
(GLSG). J Clin Oncol 2005;23 (9):1984-92.
Moskowitz AJ, Perales MA, Kewalramani T, Yahalom J, Castro-Malaspina H, Zhang Z, et al. 
Outcomes for patients who fail high dose chemoradiotherapy and autologous stem 
cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J 
Haematol 2009;146 (2):158-63.
Okkenhaug K, Vanhaesebroeck B. PI3K-signalling in B- and T-cells: insights from gene-
targeted mice. Biochemical Society transactions 2003;31 (Pt 1):270-4.


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Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin 
prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic 
review and meta-analysis. Leuk Lymphoma 2009;50 (5):764-72.
Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, et al. Intensified 
chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab 
for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label 
randomised phase 3 trial. Lancet 2011;378 (9806):1858-67.
Salles GA. Clinical features, prognosis and treatment of follicular lymphoma. Hematology / the 
Education Program of the American Society of Hematology. American Society of 
Hematology 2007:216-25.
Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, et al. Long-term results of 
combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority 
of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol 1987;5 
(1):27-37.
Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T, et al. Immunochemotherapy with 
rituximab and overall survival in patients with indolent or mantle cell lymphoma: 
a systematic review and meta-analysis. J Natl Cancer Inst 2007;99 (9):706-14.
Surveillance Epidemiology and End Results (SEER) Program. SEER Stat Fact Sheets: Chronic 
Lymphocytic Leukemia. Available at: 
http://seer.cancer.gov/statfacts/html/clyl.html. Accessed 12 May 2011.
Vanhaesebroeck B, Ali K, Bilancio A, Geering B, Foukas LC. Signalling by PI3K isoforms: 
insights from gene-targeted mice. Trends Biochem Sci 2005;30 (4):194-204.
Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, et al. Ofatumumab 
as single-agent CD20 immunotherapy in fludarabine-refractory chronic 
lymphocytic leukemia. J Clin Oncol 2010;28 (10):1749-55.
Williams ME, Dreyling M, Winter J, Muneer S, Leonard JP. Management of mantle cell 
lymphoma: key challenges and next steps. Clinical lymphoma, myeloma & 
leukemia 2010;10 (5):336-46.
Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Bellam N, et al. Non-
Hodgkin's lymphomas. J Natl Compr Canc Netw 2011;9 (5):484-560.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
199 EAST BLAINE STREET 
SEATTLE, W A 98102 
STUDY ACKNOWLEDGEMENT 
Final 
Amendment3 
An Open Label, Roll Over Study to Provide ldelalisib to Subjects Previously Treated with the 
Investigational PI3Ko Inhibitor, GS-9820 
Amendment 3 04 November 2016 
Trus protocol has been approved by Gilead Sciences, Inc. The foUowing signature documents 
this approval. 
PD 
Mario Maroondes, MD 
Gilead Medical Monitor 
Date I 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appeodi.ces, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designaled. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully infonned about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
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04 November 20 l6 


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Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a) Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause.  In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b) Definition of Male Fertility
For the purposes of this study, a male born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Idelalisib has insufficient data to exclude the possibility of a clinically relevant interaction with 
hormonal contraception that results in reduced contraception efficacy.  Therefore, contraceptive 
steroids are not recommended as a contraceptive method either solely or as a part of a 
contraceptive regimen.  Data from clinical pharmacokinetic interaction studies of idelalisib have 
demonstrated no adverse effect on fertility or embryo-fetal development.  However, there is no 
clinical data of idelalisib in pregnant women.  Please refer to the latest version of the 
investigator’s brochure for additional information. 
b) Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires using a highly effective 
contraceptive measure.  They must also not rely on hormone-containing contraceptives as a form 
of birth control during the study.  They must have a negative serum pregnancy test at Screening 
and a negative pregnancy test on the Baseline/Day 1 visit prior to randomization.  At minimum, a 
pregnancy test will be performed at the end of relevant systemic exposure.  In the event of a 
delayed menstrual period (over one month between menstruations), a pregnancy test must be 
performed to rule out pregnancy.  This is even true for women of childbearing potential with 
infrequent or irregular periods.  They must also agree to one of the following from Screening 
until 30 days after the end of relevant systemic exposure.


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Complete abstinence from intercourse of reproductive potential.  Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual lifestyle.
Or
Consistent and correct use of 1 of the following methods of birth control listed below. 

Intrauterine device (IUD) with a failure rate of <1% per year

Tubal sterilization

Ensure micro-insert system (provided confirmation of success 3 months after procedure)

Vasectomy in the male partner (provided that the partner is the sole sexual partner and had 
confirmation of surgical success 3 months after procedure)

Barrier methods (one female barrier and one male barrier must be used in combination)
Female barriers: Diaphragm with spermicide or Cervical cap with spermicide
Male barriers: Male condom (with or without spermicide)
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 30 days after the end of relevant systemic exposure
3) Contraception Requirements for Male Subjects
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment until the end of relevant 
systemic exposure.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM).  Female condom and male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last idelalisib dose. Subjects who become 
pregnant or who suspect that they are pregnant during the study must report the information to 
the investigator and discontinue idelalisib immediately. Subjects whose partner has become 
pregnant or suspects she is pregnant during the study must report the information to the 
investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome 
are outlined in Section 7.6.2.1.

Prot_002.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Director 
or Clinical Program 
Manager: 
Gilead Medical 
Monitor: 
Protocol Version/Date: 
(!') GILEAU 
CLINICAL STUDY PROTOCOL 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Ko Inhibitor, GS-9820 
Gilead Sciences, Inc. 
199 East Blaine Street 
Seattle, W A 98102 
N/A 
2015-005766-39 
Lymphoid Malignancies 
GS-US-313-2120 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Original: 
Amendment 1: 
Amendment 2: 
epo 
rpo 
1PPD 
Mario Marcondes 
PPD 
PPD 
05 Januaty 2016 
28 Mru·ch 2016 
26 August 2016 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this docmnent, patticularly unpublished data, is the prope1ty or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, yom staff, and an applicable Institutional 
Review Boru·d or Independent Ethics Committee. The infmmation is only to be used by you in 
connection with authorized clinical studies of the investigational dmg described in the protocol. 
You will not disclose any of the info1mation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessa1y to obtain informed consent from those 
persons to whom the dmg may be administered. 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF IN-TEST FIGURES.......................................................................................................................................4
PROTOCOL SYNOPSIS ..............................................................................................................................................5
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS......................................................................8
1.
INTRODUCTION ..............................................................................................................................................10
1.1.
Background ............................................................................................................................................10
1.2.
Idelalisib.................................................................................................................................................10
1.3.
Rationale for This Study ........................................................................................................................11
1.4.
Benefit/Risk Assessment for the Study..................................................................................................11
1.5.
Compliance ............................................................................................................................................11
2.
OBJECTIVES.....................................................................................................................................................12
3.
STUDY DESIGN................................................................................................................................................13
3.1.
Endpoints ...............................................................................................................................................13
3.2.
Study Design..........................................................................................................................................13
3.3.
Study Treatments ...................................................................................................................................13
3.4.
Duration of Treatment............................................................................................................................13
3.5.
Discontinuation Criteria.........................................................................................................................13
3.6.
Source Data............................................................................................................................................14
3.7.
Biomarker Testing..................................................................................................................................14
4.
SUBJECT POPULATION..................................................................................................................................15
4.1.
Number of Subjects and Subject Selection ............................................................................................15
4.2.
Inclusion Criteria....................................................................................................................................15
4.3.
Exclusion Criteria...................................................................................................................................15
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................17
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................17
5.2.
Description and Handling of Study Treatments .....................................................................................17
5.2.1.
Formulation..........................................................................................................................17
5.2.2.
Packaging and Labeling .......................................................................................................17
5.2.3.
Storage and Handling...........................................................................................................17
5.2.4.
Dosage and Administration of Idelalisib..............................................................................17
5.2.5.
Dispensing............................................................................................................................18
5.2.6.
Premedication.......................................................................................................................18
5.2.7.
Administration Instructions..................................................................................................18
5.2.8.
Dosing Schedule...................................................................................................................18
5.2.9.
Dose Levels..........................................................................................................................18
5.2.10.
Idelalisib Dose Adjustments.................................................................................................19
5.3.
Prior and Concomitant Medications.......................................................................................................23
5.3.1.
Anticancer or Experimental Therapies Other than Investigational 
Treatments............................................................................................................................23
5.3.2.
Antibiotics/ PJP Prophylaxis................................................................................................23
5.3.3.
Antidiarrheals.......................................................................................................................25
5.3.4.
Corticosteroids .....................................................................................................................25
5.3.5.
Granulocyte Colony-Stimulating Factors and Erythropoietin..............................................25
5.3.6.
Drugs that Alter CYP3A-Dependent Metabolism................................................................25


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5.3.7.
Drugs that undergo CYP3A-Dependent Metabolism...........................................................26
5.3.8.
Immunization .......................................................................................................................26
5.3.9.
Ultraviolet Exposure ............................................................................................................26
5.3.10.
Surgery .................................................................................................................................26
5.4.
Accountability for Idelalisib...................................................................................................................27
5.4.1.
Overdose Precautions...........................................................................................................27
5.4.2.
Inadvertent Exposure and Spill Precautions.........................................................................27
5.4.3.
Investigational Medicinal Product Return or Disposal.........................................................28
5.5.
Discontinuation from Study ...................................................................................................................28
6.
STUDY PROCEDURES ....................................................................................................................................29
6.1.
Subject Enrollment.................................................................................................................................29
6.1.1.
Subject Recruitment .............................................................................................................29
6.1.2.
Subject Compensation for Participation...............................................................................29
6.1.3.
Screening Visit .....................................................................................................................29
6.2.
Treatment Assessments..........................................................................................................................29
6.2.1.
Clinical Evaluation...............................................................................................................30
6.2.2.
Laboratory Assessments.......................................................................................................30
6.3.
End of Study...........................................................................................................................................31
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................34
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................34
7.1.1.
Adverse Events.....................................................................................................................34
7.1.2.
Serious Adverse Events........................................................................................................34
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................35
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................35
7.2.1.
Assessment of Causality for Idelalisib and Procedures........................................................35
7.2.2.
Assessment of Severity ........................................................................................................36
7.3.
Evaluation, Intervention, and Drug Discontinuation for Specific Adverse Events or 
Conditions ..............................................................................................................................................37
7.3.1.
Dermatological Events (Idelalisib).......................................................................................37
7.3.2.
Gastrointestinal Events.........................................................................................................37
7.3.3.
Hepatic Events......................................................................................................................38
7.3.4.
Hematological and Immunological Events...........................................................................39
7.3.5.
Pulmonary Events ................................................................................................................39
7.3.6.
Secondary Malignancies.......................................................................................................40
7.3.7.
Tumor Lysis Syndrome........................................................................................................40
7.4.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................40
7.4.1.
Serious Adverse Event (eSAE) Reporting Process ..............................................................41
7.5.
Gilead Reporting Requirements.............................................................................................................41
7.5.1.
Reporting of Adverse Events Relating and Other Anticipated Medical 
Events in the Study Population ............................................................................................42
7.5.2.
Toxicity Management...........................................................................................................42
7.6.
Special Situations Reports......................................................................................................................42
7.6.1.
Definitions of Special Situations..........................................................................................42
7.6.2.
Instructions for Reporting Special Situations.......................................................................43
8.
STATISTICAL CONSIDERATIONS................................................................................................................45
8.1.
Analysis Objectives................................................................................................................................45
8.2.
Safety Endpoints ....................................................................................................................................45
8.3.
Analysis Sets..........................................................................................................................................45
8.4.
Analysis Methods...................................................................................................................................45


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8.5.
Adverse Events.......................................................................................................................................45
9.
RESPONSIBILITIES..........................................................................................................................................46
9.1.
Investigator Responsibilities ..................................................................................................................46
9.1.1.
Good Clinical Practice..........................................................................................................46
9.1.2.
Independent Ethics Committee (IEC) Review and Approval...............................................46
9.1.3.
Informed Consent.................................................................................................................46
9.1.4.
Confidentiality......................................................................................................................47
9.1.5.
Study Files and Retention of Records ..................................................................................47
9.1.6.
Case Report Forms...............................................................................................................48
9.1.7.
Drug Accountability and Return ..........................................................................................49
9.1.8.
Inspections............................................................................................................................49
9.1.9.
Protocol Compliance............................................................................................................49
9.2.
Sponsor Responsibilities ........................................................................................................................49
9.2.1.
Protocol Modifications.........................................................................................................49
9.2.2.
Communications with Regulatory Authorities.....................................................................50
9.2.3.
Study Report and Publications .............................................................................................50
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................50
9.3.1.
Payment Reporting...............................................................................................................50
9.3.2.
Access to Information for Monitoring..................................................................................51
9.3.3.
Access to Information for Auditing or Inspections ..............................................................51
9.3.4.
Study Discontinuation..........................................................................................................51
10.
REFERENCES ...................................................................................................................................................52
11.
APPENDICES ....................................................................................................................................................55
Appendix 1.
Investigator Signature Page....................................................................................................56
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................57
LIST OF IN-TEXT TABLES
Table 5-1.
Idelalisib Dose Levels ............................................................................................................19
Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}.....................................................20
Table 6-1.
Schedule of Study Procedures................................................................................................33
Table 7-1.
Grading of Adverse Event Severity........................................................................................36
LIST OF IN-TEST FIGURES
Figure 7-1.
Kaplan-Meier Time to Diarrhea or Colitis .............................................................................38


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
199 East Blaine Street
Seattle, WA 98102
Study Title: 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Kδ Inhibitor, GS-9820
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
Not Applicable
2015-005766-39
Study Centers 
Planned:
2 centers in the Netherlands
Objectives:
The primary objective of this study is as follows:

To provide open-label idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure who have had
objective evidence of clinical benefit defined as at least stable 
disease on imaging assessed by an independent review committee 
(IRC) and no toxicities prior to enrollment in this study that 
would preclude initiating therapy with idelalisib. Idelalisib and 
GS-9820 are both in the class of agents that inhibit PI3Kδ and as 
such this exchange of class for class agent is warranted and 
acceptable.
Study Design:
This study is an open-label, rollover study to provide idelalisib to 
subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure.
Number of Subjects 
Planned:
Approximately 6 subjects
Target Population:
Subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure who have objective evidence of clinical benefit defined 
as at least stable disease on imaging assessed by the IRC at final 
response assessment prior to enrollment in this study.


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Duration of 
Treatment:
Subjects will be treated until withdrawal from study drug, progressive 
disease, intolerable study drug-related toxicity, pregnancy, substantial 
noncompliance with study procedures, or study discontinuation.
Idelalisib administration should only be continued in subjects with a 
positive benefit-risk profile assessment as per the investigator.
Diagnosis and Main 
Eligibility Criteria:
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be 
eligible for participation in this study:
1) Receiving GS-9820 in Study GS-US-315-0102 with objective 
evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC at the time of Study GS-US-315-0102
closure
2) For female subjects of childbearing potential, willingness to use a 
protocol recommended method of contraception during 
heterosexual intercourse from the signing of informed consent 
throughout the study treatment period and up to 30 days from the 
last dose of idelalisib (see Appendix 2)
3) For male subjects of reproductive potential having intercourse 
with females of childbearing potential, willing to use a protocol 
recommended method of contraception during heterosexual 
intercourse and to refrain from sperm donation throughout the 
study treatment period and for 90 days following discontinuation 
of idelalisib (see Appendix 2)
4) Willingness to comply with scheduled visits, drug administration 
plan, imaging studies, laboratory tests, other study procedures, 
and study restrictions, including mandatory prophylaxis for 
Pneumocystis jirovecii pneumonia (PJP). Note: Psychological, 
social, familial, or geographical factors that might preclude 
adequate study participation should be considered.
5) Evidence of a personally signed informed consent indicating that 
the subject is aware of the neoplastic nature of their disease and 
has been informed of the procedures to be followed, the 
experimental nature of the therapy, alternatives, potential benefits, 
possible side effects, potential risks and discomforts, and other 
pertinent aspects of study participation.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not
eligible to be enrolled in this study:
1) Known hypersensitivity or intolerance to any of the active 
substances or excipients in the formulation of idelalisib.


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2) Toxicities that would preclude initiating therapy with idelalisib 
prior to enrollment (eg, history of drug-induced pneumonitis, 
ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding
5) Ongoing infection, treatment, or prophylaxis for CMV within the 
past 28 days.
Study Procedures/
Frequency:
All subjects will receive idelalisib 150 mg taken orally, twice per day 
(BID) continuously. Subjects will undergo disease assessments and 
receive medical care per institutional standards of care.
Test Product, Dose, 
and Mode of 
Administration:
Idelalisib: 150 mg taken orally BID starting on Day 1 and 
administered continuously thereafter.
Reference Therapy, 
Dose, and Mode of 
Administration:
None
Criteria for 
Evaluation:
Safety:
Overall safety profile characterized by the type, frequency, severity, 
timing of onset, duration, and relationship to study therapy of ≥Grade 
3 adverse events (AEs), serious adverse events (SAEs), and deaths.
Efficacy:
Investigator response assessments
Statistical Methods:
Safety will be assessed by incidence of ≥ Grade 3 AEs, SAEs, and 
deaths. Efficacy will be evaluated by investigator response 
assessments. Both safety and efficacy will be assessed using data 
collected from subjects who received at least 1 dose of idelalisib. All 
analyses will be limited to descriptive summaries and listings.
Sample Size:
Up to 6 subjects
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
-HCG
beta human chorionic gonadotropin
BID
bis in die (twice daily)
CFR
Code of Federal Regulations
CLL
chronic lymphocytic leukemia
CRO
contract research organization
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DSPH
Drug Safety and Public Health
eCRF
electronic case report form
EOS
end of study
EU
European Union
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
G-CSF
granulocyte colony-stimulating factor
GCP
good clinical practice
GM-CSF
granulocyte-macrophage colony-stimulating factors
HLT
High-Level Term
HMG-CoA
3-hydroxy-3-methyl-glutaryl-Coenzyme A
IB
investigator’s brochure
ICH
International Conference on Harmonisation
iNHL
indolent non-Hodgkin lymphoma
IEC
independent ethics committee
IUD
intrauterine device
MCL
mantle cell lymphoma
NHL
non-Hodgkin lymphoma
PI3K
phosphatidylinositol 3-kinase
PDE5
phosphodiesterase-5
PJP
pneumocystis jirovecii pneumonia
SAE
serious adverse event
SJS
Stevens-Johnson Syndrome
SOC
system organ class


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SOP
standard operating procedure
SADR
serious adverse drug reaction
SUSAR
suspected unexpected serious adverse reactions
TEN
Toxic Epidermal Necrolysis
ULN
upper limit of normal


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1.
INTRODUCTION
1.1.
Background
B-cell lymphoid malignancies comprise the most common hematological malignancies 
{Surveillance Epidemiology and End Results (SEER) Program 2011}. These cancers arise from 
the accumulation of monoclonal B lymphocytes in lymph nodes and often in organs such as 
blood, bone marrow, lymph nodes, spleen, and liver. Among the variants of these cancers are 
non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), indolent 
non Hodgkin lymphoma (iNHL), and mantle cell lymphoma (MCL), as well as chronic 
lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL). These disorders are characterized 
by lymphadenopathy that is frequently disturbing for patients and can sometimes induce life 
threatening organ dysfunction; patients may also have constitutional symptoms (fevers, night 
sweats, and/or weight loss) and fatigue {Diehl et al 2004, Dighiero et al 2008, Salles 2007, 
Williams et al 2010}. 
The goal of therapy for these diseases is to induce tumor regression and delay tumor progression 
in order to control disease-related complications and potentially extend life. Patients who require 
treatment are commonly given chemotherapeutic and/or immunotherapeutic agents {Eichhorst et 
al 2010, Friedberg 2011, Gribben et al 2011, Hoppe et al 2008, Jost 2007, Zelenetz et al 2011}. 
Among patients with iNHL, CLL, and MCL, front line combination therapies can be effective in 
providing durable remissions {Hallek et al 2010, Lenz et al 2005, Recher et al 2011, Santoro et 
al 1987, Schulz et al 2007}. In DLBCL and HL, such front-line regimens can be curative in the 
majority of patients {Kuruvilla 2009, Recher et al 2011, Santoro et al 1987}. However, most 
treated patients with iNHL, CLL, and MCL will eventually experience disease relapse. Some 
patients with DLBCL or HL will experience recurrent disease even with initial induction therapy 
and later salvage therapy. For any of these cancers, further sequential therapies are given in an 
attempt to control disease manifestations. Despite use of agents with differing mechanisms of 
action, progressive resistance to treatment develops. Patients with progressive disease have a 
poor prognosis; median survival for these groups of patients is generally ≤2 years {Di Bella et al 
2010, Friedberg 2011, Goy et al 2009, Hess et al 2009, Keating et al 2002, Moskowitz et al 2009, 
Wierda et al 2010}. Novel mechanisms of action are needed to offer additional treatment options 
for patients with lymphoid malignancies who are experiencing progressive lymphadenopathy or 
symptoms due to disease progression.
1.2.
Idelalisib
Idelalisib (Zydelig®) was first approved in the United States on July 23, 2014 for the treatment 
of relapsed CLL, follicular lymphoma (FL), and small lymphocytic lymphoma (SLL), followed 
by approval in the EU on September 18, 2014 (centrally authorized). To date, Zydelig is 
currently approved in 37 countries. Refer to local labeling for the approved indication 
statements.


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Idelalisib is a potent competitive inhibitor of the adenosine triphosphate (ATP) binding site of 
the phosphatidylinositol 3 kinase (PI3K) p110δ catalytic domain, which has been shown to be 
prominently expressed in cells of hematopoietic origin {Okkenhaug et al 2003, Vanhaesebroeck 
et al 2005}. The effects of p110δ on lymphocyte activation/function, cellular proliferation, and 
protection from apoptosis provide the rationale for targeting this isoform as a therapy for 
hematologic malignancies.
Further details on the preclinical pharmacology, toxicology, metabolism and pharmacokinetics 
(PK) of idelalisib can be found in the idelalisib Investigator’s Brochure (IB).
1.3.
Rationale for This Study
Study GS-US-315-0102 is being conducted to evaluate the safety and efficacy of GS-9820, a 
second generation PI3Kδ inhibitor in subjects with iNHL, DLBCL, MCL, HL, or CLL. GS-9820 
was anticipated to offer similar efficacy to idelalisib in lymphoid malignancies while offering a 
more favorable safety profile than idelalisib. The development of GS-9820 has been 
discontinued by Gilead Sciences due to demonstration of a similar safety profile to idelalisib. 
Manufacture of the investigational agent GS-9820 has been discontinued, and will no longer be 
available to the ongoing subjects in Study GS-US-315-0102.  
This rollover study provides access to idelalisib for eligible subjects receiving GS-9820 in Study 
GS-US-315-0102 at the time of study closure who have had objective evidence of clinical benefit 
defined as at least stable disease on imaging assessed by the independent review committee 
(IRC) and no toxicities prior to enrollment in this study that would preclude initiating therapy 
with idelalisib.  Subjects will be allowed to receive treatment on this study until unacceptable 
toxicity, progressive disease, study withdrawal, or death occurs.
1.4.
Benefit/Risk Assessment for the Study
Subjects enrolled in this study have a serious life-threatening disease, with limited treatment 
options. Without treatment their disease will progress and ultimately be fatal. Transitioning 
subjects from GS-9820 to idelalisib, a similar agent in class that has shown proof of clinical 
activity and has received regulatory approval for the treatment of relapsed CLL and iNHL 
{Gilead Sciences Limited 2015}, is rational as described in Section 1.3 of this protocol; 
therefore, subjects enrolled in this study may derive clinical benefit defined as an improvement 
in disease control such as response to study treatment. The risks that may accompany study 
treatment are related to the identified and potential toxicities of treatment with idelalisib and are 
described in Section 5 of this protocol and in the ICF. The management of these toxicities is 
described in Table 5-2. Taken together, there is a positive benefit/risk for initiating study 
treatment with idelalisib in subjects previously treated with GS-9820.
1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To provide idelalisib, a marketed PI3Kδ inhibitor, in lieu of GS-9820, an investigational 
second generation PI3Kδ inhibitor, to subjects receiving GS-9820 in Study GS-US-315-0102
at the time of study closure who have had objective evidence of clinical benefit defined as at 
least stable disease on imaging assessed by the IRC and no toxicities prior to enrollment in 
this study that would preclude initiating therapy with idelalisib. Idelalisib and GS-9820 are 
both in the class of agents that inhibit PI3Kδ and as such this exchange of class for class 
agent is warranted and acceptable.


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3.
STUDY DESIGN
3.1.
Endpoints
There is no primary endpoint of this study.
3.2.
Study Design
This study is an open-label, rollover study to provide idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure.
3.3.
Study Treatments
All subjects will receive idelalisib 150 mg taken orally, twice per day (BID) continuously. 
3.4.
Duration of Treatment
Treatment will continue until unacceptable toxicity, disease progression, study discontinuation 
(outlined below), or death occurs.
3.5.
Discontinuation Criteria
Subjects may be withdrawn from the study under the following circumstances:

The subject withdraws consent to participate in the study

The subject permanently discontinues idelalisib treatment for any reason

The subject experiences a toxicity that necessitates permanent discontinuation of idelalisib
treatment

The subject has progressive disease 

The subject does not comply with the requirements of the protocol (eg initiation of a 
non-protocol anti-tumor treatment)

Gilead, a regulatory agency, or an independent ethics committee (IEC) discontinues the study
The reason for withdrawal will be recorded in the eCRF.


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3.6.
Source Data
Electronic data (ie, diagnostic machines that transcribe data directly to a database, or data entered 
directly into an Electronic Medical Record system) is considered source data, provided the data 
is not recorded directly on the CRF/eCRF, and provided there is a clear audit trail in the 
electronic record(s). No data will be recorded directly on the CRF/eCRF, and any data recorded 
directly on the CRF/eCRF will not be considered source data.
3.7.
Biomarker Testing
There will be no biomarker testing in this study.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 6 subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure are anticipated.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Receiving GS-9820 in Study GS-US-315-0102 with objective evidence of clinical benefit 
defined as at least stable disease on imaging assessed by the IRC at the time of Study 
GS-US-315-0102 closure
2) For female subjects of childbearing potential, willingness to use a protocol recommended 
method of contraception during heterosexual intercourse from the signing of informed 
consent throughout the study treatment period and up to 30 days from the last dose of 
idelalisib (see Appendix 2)
3) For male subjects of reproductive potential having intercourse with females of childbearing 
potential, willing to use a protocol recommended method of contraception during 
heterosexual intercourse and to refrain from sperm donation throughout the study treatment 
period and for 90 days following discontinuation of idelalisib (see Appendix 2)
4) Willingness to comply with scheduled visits, drug administration plan, imaging studies, 
laboratory tests, other study procedures, and study restrictions, including mandatory 
prophylaxis for Pneumocystis jirovecii pneumonia (PJP). Note: Psychological, social, 
familial, or geographical factors that might preclude adequate study participation should be 
considered.
5) Evidence of a personally signed informed consent indicating that the subject is aware of the 
neoplastic nature  of their disease and has been informed of the procedures to be followed, 
the experimental nature of the therapy , alternatives, potential benefits, possible side effects, 
potential risks and discomforts, and other pertinent aspects of study participation.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not eligible to be enrolled in this 
study:
1) Known hypersensitivity or intolerance to any of the active substances or excipients in the 
formulation of idelalisib.


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2) Toxicities that would preclude initiating therapy with idelalisib prior to enrollment
(eg history of drug-induced pneumonitis, ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding.
5) Ongoing infection, treatment, or prophylaxis for CMV within the past 28 days.


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5. 
INVESTIGATIONAL MEDICINAL PRODUCTS 
5.1. 
Randomization, Blinding and Treatment Codes 
The study is open-label and non-randomized. 
5.2. 
Description and Handling of Study Treatments 
5.2.1. 
Formulation 
Final 
Amendment 2 
Idelalisib 150 mg tablets aTe pink, oval-shaped and debossed with ''GSI' ' on one side and 
" 150" on the other. The 100 mg tablets are orange, oval-shaped and debossed with "GSI" on 
one side and '' 100'' on the other. All tablets ru·e film-coated, and include the following inactive 
exci ients: PPD 
5.2.2. 
Packaging and Labeling 
Idelalisib tablets, 150 mg or 100 mg, ru·e packaged in white, high density polyethylene (HDPE) 
bottles. Each bottle contains 60 tablets and polyester packing material. Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an induction-
sealed and aluminum-faced liner. 
Idelalisib to be distributed to centers in the US and other pruticipating countries shall be labeled 
to meet applicable requirements of the United States Food and Drug Administration (FDA), EU 
Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal Products), 
ruHJ/or other local regulations. 
5.2.3. 
Storage and Handling 
Idelalisib should be stored at controlled room temperature of 25°C (77°F); excursions are 
pennitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the 
label. Until dispensed to the subjects, all bottles of study <hugs should be stored in a securely 
locked area, accessible only to authorized site personnel. 
To ensure the stability and proper identification, study <h·ug should not be stored in a container 
other than the container in which they were supplied. Consideration should be given to handling, 
prepru·ation, and disposal through measures that minimize <hug contact with the body. Appropriate 
precautions should be followed to avoid direct eye contact or exposure when handling. 
5.2.4. 
Dosage and Administration of Idelalisib 
Idelalisib f01mulated drug product of 100 and 150 mg strengths has been manufactured for 
clinical trials and will be provided to the subject to be taken at home. Subjects should be 
instructed to take the doses with water. Idelalisib may be taken with or without food. Missed 
doses should not be taken unless it is within 6 hours of the scheduled dosing and vomited doses 
should be retaken only if the tablet is visible in the vomitus. 
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Idelalisib will be taken twice daily. Idelalisib should be taken at approximately the same times 
each day. Ideally, doses should be taken at approximately 12 hour intervals as instructed 
(eg, at 7 AM and at 7 PM). While it is realized that variations in dosing schedule may occur in 
the outpatient setting, the prescribed regimen should be followed as closely as possible.
5.2.5.
Dispensing
The clinic staff (eg, pharmacist or other qualified person) will be responsible for dispensing 
idelalisib. It is planned that idelalisib will be dispensed at 4-week intervals through the 
first 16 weeks of treatment, at 8-weeks, and at 12-week intervals thereafter. Sufficient idelalisib
will be provided for each study period at the beginning of the period. Tablets should be 
dispensed in the original bottles provided.
The clinic staff (eg, pharmacist or other qualified person) will write the subject number on each 
bottle that is dispensed. Immediately before dispensing, the clinic staff will write the bottle 
number for each dispensed bottle in the idelalisib administration record corresponding to the 
subject number.
5.2.6.
Premedication
No specific pre-medications or supporting medications are required in conjunction with idelalisib
administration.
5.2.7.
Administration Instructions
The prescribed dose of idelalisib should be taken orally. At each dose administration, the tablet 
number corresponding to the appropriate dose of idelalisib is to be swallowed whole with 
100 to 200 mL (~4 to 8 ounces) of water. In case of breakage of the tablets in the oral cavity, 
additional water should be taken as a rinse.
Idelalisib may be taken with or without food. There are no known dietary restrictions related to 
idelalisib use.
5.2.8.
Dosing Schedule
Idelalisib will be administered on a BID schedule. Idelalisib should be taken at approximately the 
same times each day.
5.2.9.
Dose Levels
Idelalisib dose levels are shown in Table 5-1. The starting dose level will be 150 mg BID. The 
lower dose level (Dose Level -1) is provided in case a subject requires a dose modification.


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Table 5-1.
Idelalisib Dose Levels
Dose Level
Dosing Regimen
Starting
150 mg BID
-1
100 mg BID
Abbreviation: BID=twice per day
Consistent with Table 5-2, if a subject experiences an AE that is suspected to be related to 
idelalisib during the course of study, idelalisib administration may be held, as necessary, until the 
AE resolves or stabilizes to an acceptable degree (as defined in Table 5-2). Thereafter, idelalisib 
may be reinitiated at either the Starting Dose Level or at Dose Level -1 consistent with the 
instructions in Section 5.2.10. A further attempt at reinitiation of therapy at Dose Level -1 may 
be attempted if the investigator feels that a second rechallenge at that dose level is medically 
appropriate. If the subject cannot tolerate idelalisib after 2 rechallenges at Dose Level -1 for the 
same AE, then the subject should be discontinued from idelalisib treatment.
After an idelalisib dose reduction, the dose need not be re-escalated, even if there is minimal or 
no toxicity with the reduced dose. However, if the subject tolerates Dose Level -1 of idelalisib
for 4 weeks, then the dose may be increased back to Starting Dose Level, at the discretion of 
the investigator. Such a re-escalation may be particularly warranted if further evaluation reveals 
that the AE that led to the dose reduction was not related to idelalisib.
5.2.10.
Idelalisib Dose Adjustments
The dose adjustment recommendations and requirements in Table 5-2 are based on the Common 
Terminology Criteria for Adverse Events (CTCAE) grade of specific toxicities. However, 
exceptions are expected for subjects who initiate study treatment with low blood counts. Clinical 
judgment should apply, and in cases of uncertainty, the study medical monitor should be 
contacted.
The dose modification instructions in Table 5-2 focus on the types of events most commonly 
associated with idelalisib. The modifications include both recommended and required actions. 
When a modification is indicated as a recommendation, it serves as a guideline; variations from 
the recommendation may be warranted based on an investigator’s individual judgment in 
considering potential risks, benefits, and therapeutic alternatives available to each subject.


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Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}
NCI CTCAE Gradea
Idelalisib
HEMATOLOGICAL ADVERSE EVENTS
Neutropenia
Grade 2 neutropenia
Recommended Action: Maintain current dose level and schedule.
Grade 3 neutropenia
Required Action: Monitor blood counts at least weekly until ANC < Grade 2.
Recommended Action: Maintain current dose level and schedule.  
Grade 4 neutropenia
(or occurrence of 
neutropenic fever or 
infection)
Required Action: 

Withhold idelalisib.  

Monitor blood counts at least weekly until ANC ≤Grade 2
Recommended Action: 

May resume idelalisib at lower dose level when ANC grade is ≤ Grade 3

Neutropenia should be managed according to established clinical guidelines.
Thrombocytopenia
Grade 3
Recommended Action: Maintain current dose level and schedule.
Grade 4
Required Action: Withhold idelalisib for bruising or bleeding until Grade 3.
Recommended Action: May resume idelalisib at initial or reduced dose level at 
investigator discretion.
NON-HEMATOLOGICAL ADVERSE EVENT
Rash
Grade 1
Recommended Action: Maintain current dose level and schedule
Grade 2
Recommended Action: Maintain current dose level and schedule 
Grade ≥3
Required Action: Withhold idelalisib until Grade 1. 
Recommended Action: Resume at lower dose level or discontinue idelalisib at 
investigator discretion.
Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)
Any Grade
Required Action: 

Discontinue idelalisib.

Institute treatment per institutional standards.

Interrupt co-administered medications potentially associated with SJS/TEN.
Bowel Perforation
Any Grade
Required Action: Discontinue idelalisib 


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NCI CTCAE Gradea
Idelalisib
Gastrointestinal Inflammation/Diarrheab
Grade 1
Required Action: 

Obtain history of onset and duration of diarrhea, including description, 
number of stools, stool composition (e.g., watery, bloody, nocturnal), travel 
history, dietary changes and a medication review to identify possible 
diarrheogenic agents.

Perform physical examination including assessment for fever, dizziness, 
abdominal pain/cramping, and weakness (e.g., evaluate for sepsis, bowel 
obstruction, dehydration).
Recommended Action: Provide anti-diarrheal agent (eg, loperamide) and maintain 
current idelalisib dose level and schedule
Grade ≥ 2 diarrhea or 
colitis (unless clinical 
diagnosis is established 
from medical history and 
physical examination)
Required Action: 

Obtain history of onset and duration of diarrhea, including description of 
number of stools and stool composition (e.g., watery, bloody, nocturnal), 
travel history, dietary changes and a medication review to identify possible 
diarrheogenic agents.

Perform physical examination including assessment for fever, dizziness, 
abdominal pain/cramping, and weakness (e.g., evaluate for sepsis, bowel 
obstruction, dehydration).

For Grade 2 colitis or diarrhea (unless clinical diagnosis is established from 
medical history and physical examination), perform stool culture for routine 
pathogens (Salmonella, Shigella, Campylobacter species, test for Clostridium 
difficile toxin, Rotavirus, Cytomegalovirus (CMV), Adenovirus), ova and 
parasites (Cryptosporidium parvum, Isospora belli, Enterocytozoon bieneusi, 
Septata intestinalis, Strongyloides, Microsporidia, Entamoeba histolytica, 
Cyclospora), and Giardia antigen. 
Recommended Action: Provide anti-diarrheal agent (eg, loperamide) and maintain 
current idelalisib dose level and schedule
Grade ≥ 3 diarrhea or 
colitis or persistent Grade 
2 diarrhea or colitis 
without clear etiology
Required Action: 

Dosing: Withhold idelalisib

Consider anti-diarrheal (eg, loperamide) and/or addition of anti-inflammatory 
agent (eg, sulfasalazine, budesonide).

Obtain history of onset and duration of diarrhea, including description, 
number of stools, stool composition (e.g., watery, bloody, nocturnal), travel 
history, dietary changes and a medication review to identify possible 
diarrheogenic agents.

Perform physical examination including assessment for fever, dizziness, 
abdominal pain/cramping, and weakness (e.g., evaluate for sepsis, bowel 
obstruction, dehydration).

For Grade 3 colitis or diarrhea (unless clinical diagnosis is established from 
medical history and physical examination), perform stool culture for routine 
pathogens (Salmonella, Shigella, Campylobacter species, testing for 
Clostridium difficile toxin, Rotavirus, Cytomegalovirus (CMV), 
Adenovirus), ova and parasites (Cryptosporidium parvum, Isospora belli, 
Enterocytozoon bieneusi, Septata intestinalis, Strongyloides, Microsporidia, 
Entamoeba histolytica, Cyclospora), and Giardia antigen.


Idelalisib 
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NCI CT CAE Grad£>• 
ld£>1alisib 
Recommended Action: 
Final 
Amendment 2 
• 
Dosing: At Grade ~1 , may resmne at lower dose level or discontinue idelalisib 
at investigator discretion. 
• 
Endoscopy with biopsy is strongly recommended to assess by rnr ...... -----. 
immm10histochemis L(!!!C and PCR for CMV, Adenovims 
• 
Provide anti-dianheal agent ( eg, loperamide) and maintain cunent idelalisib 
dose level and schedule 
H£>patic Adv£>rs£> Ev£>nts (elevations in ALT, AST, or bilirubin) 
Gradeg 
(ALT/AST:::; 3xULN) 
(Bilimbin:::; 1.5xULN) 
Grade 2 
(ALT/AST > 3-5xULN) 
(B ilimbin > 1. 5- :::; 
3xULN) 
Grade 3 
(ALT/AST>5-20xULN) 
(Bilimbin > 3-lOxULN) 
Grade 4 
(ALT/AST>20xULN) 
(Bilimbin > lOxULN) 
Recommended Action: Maintain ctUTent dose level and schedule. 
Recommended Action: Maintain current dose level and schedule 
Recommended Action: Monitor ALT, AST, ALP, and bilirubin at least lx per week 
tmtil all abnonnalities are Grade ::::;1; thereafter, maintain Ctlll'ent dose level. 
Recommended Action: Withhold idelalisib. 
Required Action: 
• 
Monitor ALT, AST, ALP, and bilirubin at least lx per week m1til all 
abnormalities are Grade :::;1. 
• 
Ifbilimbin abnom1ality is Grade <3, resmne idelalisib at same dose level. If 
bilimbin abnonnality is Grade 23, resume at lower dose level. 
Required Action: 
• 
Withhold idelalisib. 
• 
Monitor ALT, AST, ALP, and bilirubin at least lx per week tmtil all 
abnormalities are Grade :::;1. 
• 
If bilirubin abnormality is Grade 4, discontinue idelalisib. 
Recommended Action: Ifbilirubir1 abnonnality is Grade <4, resume study dmg at 
lower dose level. 
Pneumonitis (dyspnea, cough, hypoxia without obvious infectious cause) 
Grade :::;1 
Grade~2 
CONFIDENTIAL 
Recommended Action: Withhold idelalisib until resolution to baseline. May resume at 
lower dose level or discontinue idelalisib at investigator discretion. 
Required Action: 
• 
Discontinue idelalisib. 
Recommended Action: 
• 
Consider bronchoscopy to evaluate for PJP, CMV and other organisms 
(bacterial and viral) 
• 
Consider treatment with systemic corticosteroids. 
• 
Consider empir-ic treatment of pneumocystis if bronchoscopy is 
contraindicated 
• 
Upon resolution, may resume idelalisib at lower dose level at investigator 
discretion and /Gilead medical monitor agreement 
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NCI CTCAE Gradea
Idelalisib
Pneumocystis jirovecci pneumonia (PJP)
Any Grade
Required Action: Discontinue idelalisib
Unequivocal CMV infectionc
Any Grade
Required Action: 

Interrupt idelalisib upon unequivocal clinical or laboratory evidence of CMV 
infection.

Treat according to established clinical guidelines.

If the benefits of resuming idelalisib are judged to outweigh the risks, 
consideration should be given to administering pre-emptive CMV therapy.
Other Nonhematological Adverse Events
Grade 2
Recommended Action: Maintain current dose level and schedule
Grade 3
Recommended Action: Withhold idelalisib until Grade 1. May resume idelalisib at 
initial or lower dose level or discontinueidelalisib at investigator discretion.
a
CTCAE, Version 4.03.
b
See section 6.2. and 7.3.2. for additional requirements regarding an AE of diarrhea
c
CMV should be diagnosed using clinical or laboratory criteria per established institutional standard
Abbreviations: ALP=alkaline phosphatase, ALT=alanine aminotransferase, ANC=absolute neutrophil count, 
AST=aspartate aminotransferase, CTCAE=Common Terminology Criteria for Adverse Events, CMV=cytomegalovirus,
G-CSF=granulocyte-colony-stimulating factor, NCI=National Cancer Institute, ULN=upper limit of normal
5.3.
Prior and Concomitant Medications
If considered necessary for the subject’s well-being, drugs for concomitant medical conditions or 
for symptom management may be given at the discretion of the investigator.
Any concomitant medications prescribed as a therapeutic intervention for or resulting in an AE 
or SAE during the course of the study and the reason for use should be recorded on the eCRFs.
5.3.1.
Anticancer or Experimental Therapies Other than Investigational 
Treatments
Except for corticosteroids, no other anticancer therapies (including chemotherapy, radiation, 
antibody therapy, immunotherapy, or other experimental therapies) of any kind are permitted. 
Subjects are not allowed to participate concurrently in any other therapeutic clinical study.
5.3.2.
Antibiotics/ PJP Prophylaxis
5.3.2.1.
Infectious Events
Patients with lymphoid cancers receiving idelalisib have developed serious and fatal infections 
during therapy. Opportunistic infections, most notably Pneumocystis jirovecii pneumonia (PJP) 
and CMV infection, have most frequently occurred within the first 6 months of treatment with 
idelalisib and are increased in the context of concurrent myelosuppressive therapy such as 
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Subjects must receive trimethoprim-sulfamethoxazole or other established prophylaxis for PJP
throughout the course of idelalisib treatment, and for 2 to 6 months following the last dose of
idelalisib.  Prophylaxis must continue until the CD4+ T-cell count is documented to be 
>200 cells/mcL after idelalisib treatment ends. Subjects must permanently discontinue idelalisib 
upon diagnosis of PJP.
CMV surveillance for active disease (quantitative PCR or PP65 antigen) must be conducted 
approximately every 4 weeks throughout the course of idelalisib treatment. CMV viral load 
testing should be performed from the same specimen type whenever possible and caution should 
be exercised when comparing CMV viral load results across different testing centers. If 
unequivocal clinical or laboratory evidence of CMV infection is present, the subject must 
interrupt idelalisib treatment and undergo effective antiviral treatment according to established 
clinical guidelines. If the benefits of resuming idelalisib are judged to outweigh the risks, 
consideration should be given to administering pre-emptive CMV therapy.
In high-risk subjects (history of recurrent infection, allogeneic transplant, treatment with 
alemtuzumab, hypogammaglobulinemia) other infection prophylaxis should be considered per 
consensus guidelines. Administration of intravenous immunoglobulin is permitted per standard 
institutional practice {Raanani et al 2009}. For subjects who develop an infection, appropriate 
medical therapy should be instituted in a timely manner.
Trimethoprim sulfamethoxazole is rated a Pregnancy category C agent.  In rats, oral doses of 
533 mg/kg or 200 mg/kg produced teratologic effects manifested mainly as cleft palates.
One survey found no congenital abnormalities in 35 children whose mothers had received oral
sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter. Because 
sulfamethoxazole and trimethoprim may interfere with folic acid metabolism it should be used 
during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Dapsone is rated a Pregnancy Category C agent.  Extensive, but uncontrolled experience and 
two published surveys on the use of Dapsone in pregnant women have not shown that Dapsone 
increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can 
affect reproduction capacity. Because of the lack of animal studies or controlled human 
experience, Dapsone should be given to a pregnant woman only if clearly needed. Dapsone is 
excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates. 
Because of the potential for tumorgenicity shown for Dapsone in animal studies a decision 
should be made whether to discontinue nursing or discontinue the drug taking into account the 
importance of drug to the mother.
Atovaquone is rated a Pregnancy Category C agent.  Atovaquone is teratogenic and did not cause 
reproductive toxicity in rats at plasma concentrations up to 2 to 3 times the estimated human 
exposure. Atovaquone can cause maternal toxicity in rabbits at plasma concentrations that were 
approximately one half the estimated human exposure. Mean fetal body lengths and weights 
were decreased and there were higher numbers of early resorption and post-implantation loss per 
dam. It is not clear whether these effects are caused by atovaquone directly or are secondary to 
maternal toxicity. Concentrations of atovaquone in rabbit fetuses averaged 30% of the concurrent 


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maternal plasma concentrations. There are no adequate and well-controlled studies in pregnant 
women. Atovaquone should be used during pregnancy only if the potential benefit justifies the 
potential risk to the fetus. It is not known whether atovaquone is excreted into human milk. 
Because many drugs are excreted into human milk, caution should be exercised when 
Atovaquone is administered to a nursing woman. In a rat study, atovaquone concentrations in the 
milk were 30% ofthe concurrent atovaquone concentrations in the maternal plasma. 
Aerosolized Pentamidine (NebuPent) is a Pregnancy Category C agent. There are no adequate 
and well controlled studies ofNebuPent in pregnant women. One literature report indicated that 
intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; 
teratogenicity was not observed in this study. It is unknown whether pentamidine administered 
via the aerosolized route crosses the placenta at clinically significant concentrations. It is not 
known whether NebuPent can cause fetal harm when administered to a pregnant woman. 
NebuPent should be given to a pregnant woman only if clearly needed. It is not known whether 
NebuPent is excreted in human milk. NebuPent should not be given to a nursing mother unless 
the potential benefits are judged to outweigh the unknown risks. 
5.3.3. 
Antidiarrheals 
As needed, subjects may be prescribed loperamide (Imodium® or others) or diphenoxylate and 
atropine (Lomotil®) to control diarrheal symptoms. 
5.3.4. 
Corticosteroids 
Subjects may receive topical, inhaled, enteric, or systemic corticosteroids while on study. 
5.3.5. 
Granulocyte Colony-Stimulating Factors and Erythropoietin 
Granulocyte-macrophage colony-stimulating factor (GM-CSF) should not be administered given 
the potential for GM-CSF-related inflammatory symptoms. 
G-CSF (filgrastim, PEG-filgrastim, lenograstim) may be administered in response to 
Grade 4 neutropenia or neutropenic complications; (see Table 5-2). 
While erythropoietic agents (eg, erythropoietin or darbepoetin) may be administered for 
Grade ~3 anemia, their use in this study is discouraged given the potential to confound 
assessments of improvements in bone marrow function related to idelalisib. 
5.3.6. 
Drugs that Alter CYP3A-Dependent Metabolism 
Idelalisib is metabolized to its major metabolite PO 
via aldehyde oxidase and 
cytochrome P450 3A (CYP3A). Idelalisib also undergoes minor metabolism by UDP 
glucoronosyltransferase 1-4 (UGT1A4). The AUC of idelalisib was increased 1.8 fold when 
idelalisib was coadministered with a strong CYP3A inhibitor. Therefore, if subjects are taking 
concomitant strong CYP3A inhibitors, the subject should be monitored closely for signs of 
idelalisib toxicity and the dose modifications for adverse reactions should be followed in the 
event of toxicity (see Table 5-2). 
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Additionally, idelalisib exposures are approximately 75% lower when coadministered with 
rifampin, a highly potent inducer of CYP3A. Therefore, avoid coadministration of strong 
inducers ofCYP3A (rifampin, carbamazepine, phenytoin, and St. John's wort) with idelalisib. 
5.3.7. 
Drugs that undergo CYP3A-Dependent Metabolism 
The major metabolite of idelalisib, PO 
is a reversible and time dependent inhibitor of 
CYP3A; accordingly, coadministration of idelalisib with midazolam, a probe CYP3A substrate, 
resulted in a ~5-fold increase in midazolam systemic exposure (AUC). Coadministration of 
drugs that are narrow therapeutic index CYP3A substrates with idelalisib may result in an 
increase in their systemic exposures (eg, antiarrhythmics, calcium channel blockers, 
benzodiazepines, certain HMG-CoA reductase inhibitors, phosphodiesterase-S [PDE5] 
inhibitors, warfarin). Avoid coadministration of drugs that are narrow therapeutic index CYP3A 
substrates ( eg, alfentanil, cyclosporine, sirolimus, tacrolimus, cisapride, pimozide, fentanyl, 
quinidine, ergotamine, dihydroergotamine, astemizole, terfenadine) with idelalisib. 
5.3.8. 
Immunization 
Because of its actions to inhibit PI3Ko-dependent B-cell function, high doses of idelalisib can 
impair primary or secondary responses to immunization in animals. 
The specific clinical relevance ofthese findings with idelalisib is unknown. However, for 
subjects who are at substantial risk of an infection ( eg, influenza) that might be prevented by 
immunization, consideration should be given to providing the vaccine prior to initiation of study 
therapy. 
Of note, the safety of immunization with live viral vaccines following idelalisib therapy has not 
been studied and vaccination with live virus vaccines during study treatment is not 
recommended. 
5.3.9. 
Ultraviolet Exposure 
While nonclinical findings suggest the hypothetical potential for phototoxicity in humans, 
available clinical data do not reveal a photosafety concern. Although specific clinical correlates 
for these non clinical data are not available, investigators and study subjects should be observant 
for the possibility that study participants may have exaggerated sunburn reactions ( eg, burning, 
erythema, exudation, vesicles, blistering, edema) involving areas of skin exposed to ultraviolet 
light. 
5.3.10. 
Surgery 
There are no known effects of idelalisib on coagulation or wound healing. Pending receipt of 
additional information and considering the subject's current platelet counts, idelalisib may be 
continued in the peri-procedural period in subjects who require surgery or invasive procedures. 
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5.4.
Accountability for Idelalisib
The disposition of all idelalisib should be documented from the time of receipt at the site through 
subject dispensing and return.
Study personnel must ensure that idelalisib is kept in a secure locked area with access limited to 
authorized personnel. The idelalisib must not be used outside the context of this protocol. Under 
no circumstances should the investigator or site personnel supply idelalisib to other investigators 
or clinics, or allow the idelalisib to be used other than as directed by this protocol.
The investigator and/or the responsible site personnel must maintain accurate records of the 
receipt of idelalisib shipped by Gilead Sciences or its designee, including, but not limited to, the 
date received, lot number, amount received, and the disposition of all idelalisib. Upon receipt of 
a drug shipment, the shipment must be logged into the idelalisib accountability records, these 
records must also be maintained to include the subject number to whom the idelalisib was 
dispensed and the date, quantity and lot number of the idelalisib dispensed.
Depending upon the decision of Gilead Sciences, remaining unused idelalisib supply will be 
returned to Gilead Sciences or its designee after the study is completed or will be discarded or 
destroyed at the clinical site. If the idelalisib is discarded or destroyed at the clinical site, 
standard institutional policy should be followed. Records documenting the date of idelalisib
shipping or destruction, relevant lot numbers, and amount shipped or destroyed should be 
maintained.
5.4.1.
Overdose Precautions
In Phase 1 studies, an MTD for idelalisib was not reached when administering the drug 
continuously at dose levels of 350 mg/dose BID (700 mg per day) {Coutre et al 2011, Kahl et al 
2011}. However, in this protocol, an overdose is defined as administration of more than the 
prescribed daily dose (ie, >300 mg in a single day).
The Gilead Sciences medical monitor should be contacted if an idelalisib overdose occurs. Cases 
of idelalisib overdose will result in specific reporting requirements.
5.4.2.
Inadvertent Exposure and Spill Precautions
Based on available data from nonclinical studies, idelalisib does not appear to be acutely toxic, 
genotoxic, or irritative at levels that are likely to result from inadvertent exposure to the contents 
of broken tablets. However, personnel handling the drug should use reasonable precautions to 
avoid eye contact, skin contact, inhalation, or ingestion of the idelalisib product. For further 
information regarding inadvertent exposure and spill precautions, please consult the idelalisib
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5.4.3.
Investigational Medicinal Product Return or Disposal
Subjects will be instructed to return any unused idelalisib in the original container at post 
treatment study visits. Returned medication will be reconciled by the investigator in order to 
monitor the subject’s compliance with the medication regimen. When possible, all idelalisib
returned by the subject should be retained for review by the study site monitor prior to return to 
Gilead Sciences or destruction.
5.5.
Discontinuation from Study
Subject study participation may be ended due to any of the follow reasons:

Withdrawal of consent

Objective evidence of disease progression.

Unacceptable toxicity or unable to tolerate a second rechallenge for the same AE.

Any subject who becomes pregnant or begins breastfeeding.

Initiation of non-protocol specfied anticancer therapy.

Noncompliance with idelalisib administration, study procedures, or study requirements.

The investigator may discontinue idelalisib, if it is not in the subject’s best interest to 
continue.

Any subject who is lost to follow-up.

Death

Discontinuation of study by the Sponsor, a regulatory agency, or an EC

Any subject who is diagnosed with any grade SJS or TEN, Grade ≥2 pneumonitis, or any 
grade PJP.

Any subject whose benefit-risk profile is not deemed positive by the investigator should 
discontinue study drug.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Table 6-1 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment 
6.1.1.
Subject Recruitment
This study will enroll subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure who have had objective evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC and no toxicities prior to enrollment in this study that would
preclude initiating therapy with idelalisib. The study sponsor will post a description of the study 
on the ClinicalTrials.gov website.
6.1.2.
Subject Compensation for Participation
Subjects will not be paid for participation in the study other than medical care that may be 
provided. Payments for such items as lost wages, disability, discomfort due to injury, or meals 
obtained while waiting at the clinical research center will not be provided. Through the informed 
consent process, study candidates will be notified that their insurance company could be charged 
for standard care that is a component of this research study and that subjects may be responsible 
for co-payments and deductible payments that are typical for their insurance coverage.
6.1.3.
Screening Visit
The investigator must inform each prospective subject of the nature of the study, explain the 
potential risks, and obtain written informed consent from the subject and/or a legal guardian 
prior to performing any study-related screening procedures. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (CRF/eCRF).  
All other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history CRF/eCRF.  
See Section 7 Adverse Events and Toxicity Management for additional details.
6.2.
Treatment Assessments
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all SAEs, as well as any non-serious all grade AEs on the AE case 
report form (eCRF). All other untoward medical occurrences observed during the screening 


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period, including exacerbation or changes in pre-existing conditions are considered medical 
history (not collected for this study). See Adverse Events and Toxicity Management (Section 7) 
for additional details.
While on study, the subject will return at regular intervals for the following procedures:

Evaluation of disease status per standard of care

Laboratory lab tests as outlined under section 6.2.2. 

Recording of all grade AEs and all SAEs
For an AE of Diarrhea or Colitis:
1. Obtain history of onset and duration of diarrhea, including description of number of 
stools and stool composition (eg, watery, bloody, nocturnal), travel history, dietary 
changes and a medication review to identify possible diarrheogenic agents
2. Perform physical examination including assessment for fever, dizziness, abdominal 
pain/cramping, and weakness (ie, evaluate for sepsis, bowel obstruction, dehydration)

Return of used drug supplies and dispensing of new idelalisib supply
The specific study procedures to be conducted for each subject enrolled in the study are 
presented in Table 7-1 and are described in the sections that follow.
6.2.1.
Clinical Evaluation
While on study, the subject will be followed for disease status according to standard of care. At 
each study visit the subject’s disease status will be assessed. If no change in disease status is 
identified and the subject is dispensed additional idelalisib, the most recent prior response 
documented for the study will be recorded.
6.2.2.
Laboratory Assessments
Blood samples for ALT, AST, total bilirubin will be collected at Screening, Day 1, Weeks 4, 8, 
12, 16, 168, every 12 weeks thereafter, and the End of Study (EOS) Visit.
Blood samples for CMV will be collected at Screening and every 4 weeks thereafter throughout 
study participation.
Blood samples for ANC will be collected at Screening and every 2 weeks through Week 24.
Blood samples for Pneumococcal, Haemophilus Influenzae Type B (Hib), and Tetanus titers will 
be taken at screening


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Blood samples for immune-monitoring will be collected at Screening, Weeks 4, 12 and every 
12 weeks thereafter, and the EOS Visit: 
• 
Lymphocyte subset panel using flow cytometry (immunophenotyping) 
• 
Quantitative immunoglobulins: IgG, IgM, IgA 
• 
Serum CH50 level 
6.2.2.1. 
Evaluation for Gastrointestinal Events/Colitis 
For Grade 2 colitis and diarrhea (unless clinical diagnosis is established from medical history and 
physical examination), the following testing is required: 
• 
Stool culture for routine pathogens (Salmonella, Shigella, Campylobacter species, 
Clostridium diffi.cile toxin, Rotavirus, Cytomegalovirus, Adenovirus) 
• 
Stool for Ova and Parasites (Cryptosporidium parvum, Isospora belli, Enterocytozoon 
bieneusi, Septata intestinalis, Strongyloides, Microsporidia, Entamoeba histolytica, 
Cyclospora), Giardia antigen 
For Grade 2' 3 or persistent Grade 2 colitis or diarrhea without clear etiology (eg, clostridium 
diffi.cile enterocolitis), endoscopy with biopsy is strongly recommended. All biopsy samples 
should include immunohistochemistry (IHC) and PCR for CMV, Adenovirus. 
PD 
6.2.2.2. 
Differentiation Between Small-bowel and Large-bowel Diarrhea 
Differentiation between small-bowel and large-bowel diarrhea on a clinical basis if 
recommended. If unclear, consider upper and lower tract endoscopy with biopsy. 
• 
Small bowel diarrhea is characterized by large volume diarrhea (more than one per day), 
possibly associated dehydration weight loss and paraumbilical pain. Consider an endoscopic 
small-bowel biopsy and evaluate other etiologies such as celiac disease. 
• 
Large-bowel diarrhea may present with lower pelvic pain, tenesmus, generally smaller stool 
volumes with gross blood frequently found in the stool. Consider a colonoscopic evaluation 
and biopsy. 
6.3. 
End of Study 
Subjects will be withdrawn from this study if they develop progressive disease, unacceptable 
toxicity related to idelalisib, withdraw consent, are noncompliant, or are lost to follow up or die. 
In this event, the following procedures should be performed: 
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
Return of used and unused drug supply

Recording of all Grade AEs and all SAEs

Investigator Response Assessment

Laboratory assessments as outlined in Table 6-1

Recording of the reason for withdrawal

Deaths occurring within 30 days following the last dose of idelalisib, even if occurring after 
the End of Study Visit, will be captured.


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Table 6-1.
Schedule of Study Procedures
Period
Screen
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15+
End of 
study
Week
-4
0
2
4
6
8
10
12
14
16
18
20
22
24
Q4 
weeks
Q12 
weeks
Study Day
Within
-28 days
1
14
28
42
52
70
84
98
112
126
140
154
168
Visit Window
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±2
±7
±7
Informed consent
X
Serum -HCGa
X
Pneumococcal, Hib, Tetanus titers
X
ALT/AST/total bilirubin
X
X
X
X
X
X
X
X
X
Urine pregnancy testa
X
X
X
X
X
X
X
X
ANCb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CMV surveillance
X
X
X
X
X
X
X
Xc
Immune Monitoring
X
X
X
X
X
X
Assess adverse events and SAEsd
X
X
X
X
X
X
X
X
Record concomitant 
medicationse
X
X
X
X
X
X
X
X
Idelalisib dispensing/accounting
X
X
X
X
X
X
X
X
Investigator response 
assessmentf
X
X
X
X
X
X
X
X
Abbreviations: -HCG=beta human chorionic gonadotropin, ALT=alanine aminotransferase, AST=aspartate aminotransferase, Hib = Haemophilus Influenzae Type B
a
For women of child bearing potential; Serum -HCGto be collected to be collected at screening, urine pregnancy test to be collected at visits from first dose of idelalisib to EOS
b
Absolute neutrophil count (ANC) will be monitored at least every two weeks for the first 24 weeks of idelalisib treatment
c
CMV surveillance must be conducted approximately every 4 weeks throughout the course of idelalisib treatment
d
For an AE of Diarrhea/Colitis: 1) Obtain history of onset and duration of diarrhea, including description of number of stools and stool composition, travel history, dietary 
changes and a medication review to identify possible diarrheogenic agents and 2) Perform physical examination including assessment for fever, dizziness, abdominal 
pain/cramping, and weakness
e
Concomitant medications only collected if it is related to an AE
f
Record investigator response assessment if obtained per standard of care


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Lymphocytosis

Laboratory abnormalities not requiring clinical intervention or further investigation. Such 
abnormalities will be captured as part of overall laboratory monitoring.

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
CRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)


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
In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to idelalisib interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Idelalisib and Procedures
The investigator or qualified sub-investigator is responsible for assessing the relationship to 
idelalisib therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than idelalisib. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.


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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg., venipuncture)
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the CTCAE, Version 4.03 and available at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or
Grade 5 (fatal) to describe the maximum intensity of the adverse event. For purposes of 
consistency with the CTCAE, these intensity grades are defined in Table 7-1.
Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Sign or symptom is present, but it is easily tolerated, is not expected to have a 
clinically significant effect on the subject’s overall health and well-being, does 
not interfere with the subject’s usual function, and is not likely to require 
medical attention.
Grade 2
Moderate
Sign or symptom causes interference with usual activity or affect clinical status, 
and may require medical intervention.
Grade 3
Severe
Sign or symptom is incapacitating or significantly affects clinical status and 
likely requires medical intervention and/or close follow-up.
Grade 4
Life-threatening
Sign or symptom results in a potential threat to life.
Grade 5
Fatal
Sign or symptom results in death.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events listed in Section 7.1.2.


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7.3.
Evaluation, Intervention, and Drug Discontinuation for Specific Adverse 
Events or Conditions
7.3.1.
Dermatological Events (Idelalisib)
Subjects receiving idelalisib with ≥Grade 3 rash have generally presented with a maculopapular 
rash on the trunk and extremities that is occasionally associated with fever and/or pruritus and 
responded to treatment with diphenhydramine and/or topical or oral corticosteroids. 
For subjects who develop Grade ≥3 rash for which an underlying etiology cannot be identified 
(e.g., infection, co-suspect drug), study drug must be interrupted. Severe cutaneous reactions, 
including fatal events of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), 
have been reported in subjects receiving idelalisb. Assessment of potential causal association 
between idelalisib and the occurrence of SJS or TEN has been confounded by the 
coadministration of antineoplastic agents (e.g., bendamustine, rituximab) and/or other 
concomitant medications known to be associated with SJS or TEN (e.g., allopurinol). If SJS or 
TEN is suspected, idelalisib and all coadministered medications associated with SJS or TEN 
should be interrupted and the subject treated accordingly. 
Subjects should be monitored for the development of SJS, TEN, or other severe cutaneous 
reactions and idelalisib treatment should be discontinued if such events occur.
7.3.2.
Gastrointestinal Events
Isolated cases of gastrointestinal inflammation (eg, stomatitis, colitis, cecitis) have been noted in 
subjects receiving idelalisib. Rare cases of gastrointestinal perforation have occurred, generally 
in the setting of occult carcinoma, mesenteric embolus or diverticular disease.  Study treatment 
(idelalisib/placebo) must be discontinued in subjects who experience bowel perforation
Cholangitis manifest as hyperbilirubinemia out of proportion to serum transaminase elevations 
has been observed. While disease-related factors, neutropenia, toxicity from prior therapies, 
effects of ongoing supportive care, or pre-existing cholelithiasis may have initiated such events, 
it is possible that idelalisib played a contributory role. In such subjects, rechallenge with 
idelalisib has been possible and has not been associated with other severe adverse events. 
Subjects who have developed evidence of enteritis during idelalisib therapy have been 
successfully treated with antidiarrheals (eg, loperamide) and with enteric steroidal (eg, 
budesonide) or non-steroidal (eg sulfasalazine [Azulfidine®]) anti-inflammatory agents and have 
been able to continue or resume idelalisib.
For study subjects who develop severe abdominal pain the possibility of a bowel obstruction or 
perforation should be considered. Appropriate clinical and radiographic examination should be 
performed and supportive care or surgical intervention should be considered. Upon recovery, 
rituximab may be resumed.


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7.3.2.1.
Investigation for Idelalisib Late Onset or Severe Diarrhea/Colitis
See CTCAE Version 4.03 for definitions of colitis and diarrhea.
Among idelalisib-treated patients who reported diarrhea or colitis, the median time to onset of 
any grade diarrhea or colitis was 1.9 months (range, 0.0–29.8), of grade 1 or 2 was 1.5 months 
(range, 0.0–15.2) and of grade 3 or 4 was 7.1 months (range, 0.5–29.8). Kaplan–Meier curves of 
time to onset of diarrhea or colitis are shown for all idelalisib- treated patients in Figure 7-1
{Coutre et al 2015}.
Figure 7-1.
Kaplan-Meier Time to Diarrhea or Colitis
Idelalisib-associated severe diarrhea responds poorly to antimotility agents however, median 
time to resolution ranged between 1 week and 1 month across trials following interruption of 
idelalisib treatment and, in some instances, initiation of corticosteroid treatment
{Gilead Sciences Inc 2014}.
7.3.3.
Hepatic Events
Transaminase Elevations: Consistent with observations in a dog toxicology study, reversible 
asymptomatic ALT/AST increases were also observed early in the idelalisib program in phase 1 
studies (101-02 and 101-07) in subjects with hematologic malignancies. Transaminase elevations 
generally occurred within 4 to 12 weeks of drug initiation, and resolved spontaneously over a 
period of 2 to 4 weeks with drug being continued for Grade 1 and 2 elevations and drug withheld 
for Grade 3 or 4 elevations until resolution. These early observations have been consistent with 
the ongoing experience with idelalisib treatment and transaminase elevations are now well 
characterized as most frequently asymptomatic, transient and occurring within the first 3 months 
of treatment.


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Grade 1 or 2 elevations commonly resolve despite continued idelalisib treatment and Grade 3 or 
4 elevations can be managed by withholding idelalisib. Successful rechallenge after resolution at 
either the same or lower dose level of idelalisib has been achieved in the majority of subjects. 
There has been no evidence of impaired synthetic function. Close monitoring of hepatic 
laboratory tests during therapy is important to allow for appropriate idelalisib interruption and 
reinstitution so that subjects may continue with study drug treatment.
7.3.4.
Hematological and Immunological Events
In the Phase 1 experience with idelalisib in patients with NHL and CLL, subjects with Grade 3 
neutropenia, anemia, and/or thrombocytopenia were enrolled to clinical trials. Decreased levels 
of neutrophil counts, hemoglobin, or platelet counts during idelalisib administration were largely 
due to minor fluctuations in these parameters among subjects with pre-existing hematological 
abnormalities due to disease or prior therapy. Thus, idelalisib did not appear to induce overt 
myelosuppression. Obvious patterns of drug-mediated reductions in circulating CD4+ 
lymphocyte counts or suppression of serum IgG levels were also not observed.
Treatment-emergent Grade 3 or 4 neutropenia events, including febrile neutropenia, have occurred in 
subjects treated with idelalisib. All subjects should have their blood counts monitored at least every 
2 weeks for the first 6 months of idelalisib treatment. For subjects who develop Grade 3 neutropenia, 
blood counts must be monitored at least weekly. For subjects who develop Grade 4 neutropenia, 
idelalisib must be interrupted and blood counts monitored at least weekly until ANC is ≥ 0.5 Gi/L, at 
which point, idelalisib may be resumed at a lower dose level.  Neutropenia should be managed 
according to established clinical guidelines.
No modification of any drug for changes in circulating CD4+ counts or Ig levels is planned.
7.3.5.
Pulmonary Events
Documented bacterial, fungal, viral, and pneumocystis pneumonias have been observed in 
patients receiving idelalisib, primarily in patients with CLL. Some study subjects receiving 
idelalisib alone or in combination have developed evidence of pneumonitis without documented 
pulmonary infection. 
Given the potential for infectious or drug-related pulmonary adverse events, clinicians should be 
particularly observant for evidence of respiratory events in subjects participating in this trial. 
Subjects who describe pulmonary symptoms (eg, dyspnea on exertion, cough, 
shortness of breath); manifest a decline from baseline of 5% in oxygen saturation, or 
demonstrate evidence of pulmonary inflammation (eg, focal or diffuse interstitial pattern or 
ground-glass opacities on chest CT) should be evaluated. Potential bacterial, fungal, or viral 
etiologies should be assessed. Noninfectious etiologies such as pulmonary edema or 
thromboembolism should also be considered.
As appropriate for the clinical situation and culture results, subjects should be treated empirically 
or given specific antibiotics, antifungals, or antiviral agents for a cultured organism. Supportive 
care, including oxygen or mechanical ventilation, should be provided as necessary.


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For subjects with suspected pneumonitis (eg, onset of cough, dyspenea, hypoxia and/or a diffuse 
interstitial pattern or ground-glass opacities on chest imaging without obvious infectious 
etiology), idelalisib should be interrupted (or discontinued if pneumonitis is Grade ≥2). 
Supportive care, including oxygen or mechanical ventilation, should be considered and provided 
as necessary. Consider bronchoscopy to evaluate for PJP, CMV and other organisms (bacterial 
and viral).  Consider treatment with systemic corticosteroids.  Consider empiric treatment of 
pneumocystis if bronchoscopy is contraindicated. Upon resolution, may resume idelalisib at 
lower dose level at investigator discretion and Gilead medical monitor agreement.
7.3.6.
Secondary Malignancies
Subjects receiving idelalisib for CLL or iNHL have developed pre-malignant and secondary 
malignant diseases, such as basal cell carcinoma, myelodysplastic syndrome, myeloproliferative 
disorders, and more aggressive lymphoid malignancies (eg, have had Richter transformation). 
Generally this has occurred in subjects who have received multiple previous lines of therapy and 
when idelalisib is combined with other therapies such as rituximab or bendamustine. The specific 
association of the therapeutic agents with these types of events has not been determined.
There are reports of pre-malignant and malignant diseases that have developed in subjects who 
have been treated with bendamustine, including myelodysplastic syndrome, myeloproliferative 
disorders, acute myeloid leukemia, and bronchial carcinoma. The specific association of the 
therapeutic agents with these types of events has not been determined.
7.3.7.
Tumor Lysis Syndrome
Tumor lysis syndrome has not been observed with idelalisib monotherapy. 
When idelalisib is combined with other agents known to induce tumor lysis syndrome, 
prophylaxis with agents such as allopurinol may be considered. The benefit versus risk of 
prophylactic agents must be carefully considered given a potential of increased risk of severe 
skin toxicity.
Subjects with tumor lysis syndrome should receive rapid reversal of hyperkalemia, intravenous 
hydration, antihyperuricemic agents, and appropriate cardiac and renal support, including 
dialysis as indicated. Upon recovery to baseline functioning, such subjects should continue study 
treatment including study drug (idelalisib/placebo).
7.4.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
All SAEs, regardless of cause or relationship, that occur after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) or designee as instructed. 
This also includes any SAEs resulting from protocol-associated procedures performed from 
screening onwards.


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All AEs, regardless of cause or relationship, that occur from initiation of study medication until 
30 days after last administration of idelalisib must be reported to the eCRF database as 
instructed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of idelalisib, regardless of causality, should also be reported.
All AEs should be followed up until resolution if possible. If by the last day on study (including 
the off-study medication follow-up period) the AE has not resolved, then the AE will be 
followed up until the investigator and/or Gilead Sciences determine that the subject's condition is 
stable. However, Gilead Sciences may request that certain AEs be followed until resolution.
Investigators are not obligated to actively seek SAEs after the 30 day period. However, if the 
investigator learns of any SAEs that occur after study participation has concluded and the event 
is deemed relevant to the use of idelalisib, he/she should promptly document and report the event 
to Gilead DSPH or designee as instructed.
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guidelines.
7.4.1.
Serious Adverse Event (eSAE) Reporting Process 
Site personnel record the SAE on the paper serious adverse event reporting form and submit via 
fax to Gilead DSPH within 24 hours.
All AEs and SAEs will be recorded in the CRF/eCRF database within the timelines outlined in 
the CRF/eCRF completion guideline.
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
Additional information may be requested to ensure the timely completion of accurate safety 
reports.
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/eCRF and the event description section of the SAE 
form.
7.5.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.


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Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with idelalisib. The investigator should notify the IEC of SUSAR reports as soon as is practical, 
where this is required by local regulatory agencies, and in accordance with the local institutional 
policy. 
7.5.1.
Reporting of Adverse Events Relating and Other Anticipated Medical Events 
in the Study Population
Given the endpoints of the study and in order to maintain the integrity of the study, the following 
events that are assessed as unrelated to idelalisib will not be considered SAEs:

Progression of lymphoid malignancy

Death related to progression of lymphoid malignancy

Disease progression and death from disease progression should be reported as SAEs by the 
investigator only if it is assessed that the idelalisib caused or contributed to the disease 
progression (ie, by a means other than lack of effect).  Unrelated disease progression should 
be captured on the eCRF.
These will be reported, as appropriate, in the final clinical study report and in any relevant 
aggregate safety reports.
7.5.2.
Toxicity Management 
See Table 5-2 for more information related to recommended dose modifications associated with 
toxicities. Please refer to the current idelalisib IB for information related to toxicity management.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.


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An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study to the Gilead DSPH using the pregnancy 
report form within 24 hours of becoming aware of the pregnancy.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post 
study must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH  using the pregnancy outcome 
report form. If the end of the pregnancy occurs after the study has been completed, the outcome 
should be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: 
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477. 
Pregnancies of female partners of male study subjects exposed to idelalisib must also be reported 
and relevant information should be submitted to Gilead DSPH using the pregnancy and 
pregnancy outcome forms within 24 hours. Monitoring of the subject should continue until the 
conclusion of the pregnancy. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead DSPH, fax number +1 650 522-5477
or email Safety_FC@gilead.com. 
Refer to Appendix 2 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.


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7.6.2.2.
Reporting Other Special Situations
All other special situation reports (excluding pregnancy) must be reported on the special 
situations report form and forwarded to Gilead DSPH within 24 hours of the investigator 
becoming aware of the situation. These reports must consist of situations that involve idelalisib, 
but do not apply to concomitant medications. Except for situations that result in AEs, special 
situations involving concomitant medication will not be reported. Any inappropriate use of 
concomitant medications prohibited by this protocol should not be reported as “misuse,” but may 
be more appropriately documented as a protocol deviation.
Refer to the CRF/eCRF completion guidelines for full instructions on the mechanism of special 
situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE CRF/eCRF and/or the SAE report form. Details of the symptoms 
and signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives
As noted in Section 2, the primary objective is to provide idelalisib to subjects receiving
GS-9820 in Study GS-US-315-0102 at the time of study closure who have had objective 
evidence of clinical benefit defined as at least stable disease on imaging assessed by the IRC and 
no toxicities prior to enrollment in this study that would preclude initiating therapy with 
idelalisib.
8.2.
Safety Endpoints
Safety will be assessed with endpoints including incidence of ≥Grade 3 AEs, SAEs, and deaths.
8.3.
Analysis Sets
Both safety and efficacy will be assessed using data collected from subjects who received at least 
1 dose of idelalisib.
8.4.
Analysis Methods
All the analyses will be limited to descriptive summaries and listings. Categorical variables will 
be summarized with the number and percentage of subjects in each category. Continuous 
variables will be summarized by presenting n, mean, standard deviation, median, Q1, Q3, 
minimum and maximum.
8.5.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable sub-investigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any sub-investigator’s) participation in the study. The investigator and 
sub-investigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Independent Ethics Committee (IEC) Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IEC. The investigator will not begin any study subject activities until 
approval from the IEC has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IEC any modifications made to the protocol or any accompanying material to be provided to 
the subject after initial IEC approval, with the exception of those necessary to reduce immediate 
risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IEC-approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately signed 


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and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IEC or local 
requirements. 
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form submitted to the Sponsor. NOTE: The investigator must keep a screening log showing 
codes, names, and addresses for all subjects screened and for all subjects enrolled in the trial.
Subject data will be processed in accordance with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, CRF/eCRF, idelalisib, and any other study information, 
remain the sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IEC
and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Birth dates will be collected as per local regulatory requirements, as needed

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);


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
Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of idelalisib, including dates of dispensing and 
return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 
data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), the investigator will use his/her log in 
credentials to confirm that the forms have been reviewed, and that the entries accurately reflect 
the information in the source documents. The eCRF capture the data required per the protocol 


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schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (eg data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Drug Accountability and Return
Gilead recommends that used and unused idelalisib supplies be returned to the shipping facility 
from which it came for eventual destruction. The study monitor will provide instructions for 
return. If return is not possible, the study monitor will evaluate each study center’s disposal 
procedures and provide appropriate instruction for destruction of unused idelalisib supplies. If 
the site has an appropriate standard operating procedure (SOP) for drug destruction as 
determined by Gilead QA, the site may destroy used (empty or partially empty) and unused 
idelalisib supplies in accordance with that site’s approved SOP. A copy of the site’s approved 
SOP will be obtained for central files. 
If idelalisib is destroyed on site, the investigator must maintain accurate records for all idelalisib
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the idelalisib. Upon study completion, copies of 
the idelalisib accountability records must be filed at the site. Another copy will be returned to 
Gilead.
The study monitor will review idelalisib supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to appropriately qualified personnel from Gilead Sciences or 
its representatives, to IECs, or to regulatory authority or health authority inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IEC in 
accordance with local requirements and receive documented IEC approval before modifications 
can be implemented.


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9.2.2.
Communications with Regulatory Authorities
Gilead Sciences, working either directly or through designees, will assume responsibility for 
regulatory interactions with relevant regulatory authorities. Gilead Sciences will maintain an 
IND for idelalisib in support of the study in the United States and will maintain similar 
regulatory applications with other regulatory authorities, as required for conduct of the study. In 
fulfilling this responsibility, Gilead Sciences (or a designee) will collect, assemble, and 
communicate all required regulatory documents (eg, Form FDA 1572, investigator financial 
disclosure forms, protocol and protocol amendments, investigator brochures, informed consent 
documents, annual reports) as required by regulation. Gilead Sciences (or a designee) will also 
assume responsibility for adverse event reporting to regulatory authorities as described in 
Section 7.5.
9.2.3.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). Gilead 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly 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.
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg attendance at Investigator's Meetings.  If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
CRF/eCRF.
The monitor is responsible for routine review of the CRF/eCRF at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the CRF/eCRF. The investigator agrees to cooperate with the monitor to 
ensure that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies) and IECs. In terminating the study, Gilead and the investigator will 
assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
Coutre S, Barrientos JC, Brown JR, De Vos S, Furman RR, Keating MJ, et al. Safety of idelalisib 
in B-cell malignancies: Integrated analysis of eight clinical trials [Presentation 
EHA-3983]. 20th Congress of European Hematology Association (EHA); 2015; 
Vienna, Austria. 
Coutre S, Byrd J, Furman R, Brown J, et al. Phase I study of CAL-101, an isoform-selective 
inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously 
treated chronic lymphocytic leukemia [Abstract]. 47th Annual Meeting of the 
American Society of Clinical Oncology (ASCO); 2011 June 3; Chicago, IL. 
Di Bella N, Taetle R, Kolibaba K, Boyd T, Raju R, Barrera D, et al. Results of a phase 2 study of 
bortezomib in patients with relapsed or refractory indolent lymphoma. Blood 
2010;115 (3):475-80.
Diehl V, Thomas RK, Re D. Part II: Hodgkin's lymphoma--diagnosis and treatment. Lancet 
Oncol 2004;5 (1):19-26.
Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia. Lancet 2008;371 (9617):1017-29.
Eichhorst B, Hallek M, Dreyling M. Chronic lymphocytic leukaemia: ESMO Clinical Practice 
Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21 Suppl 
5:v162-4.
Friedberg JW. New strategies in diffuse large B-cell lymphoma: translating findings from gene 
expression analyses into clinical practice. Clin Cancer Res 2011;17 (19):6112-7.
Gilead Sciences Inc. ZYDELIG® (idelalisib) tablets, for oral use. U.S. Prescribing Information. 
Foster City, CA. July 2014:
Gilead Sciences Limited. Zedelig (idelalisib) 150mg. Summary of Product Characteristics. 
Cambridge,United Kingdom. Revised  21 July.  2015:
Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Bortezomib in 
patients with relapsed or refractory mantle cell lymphoma: updated time-to-event 
analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 2009;20 
(3):520-5.
Gribben JG, O'Brien S. Update on therapy of chronic lymphocytic leukemia. J Clin Oncol 
2011;29 (5):544-50.


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Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of 
rituximab to fludarabine and cyclophosphamide in patients with chronic 
lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376 
(9747):1164-74.
Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, et al. Phase III study 
to evaluate temsirolimus compared with investigator's choice therapy for the 
treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27 
(23):3822-9.
Hoppe RT, Advani RH, Ambinder RF, Bierman PJ, Bloomfield CD, Blum K, et al. Hodgkin 
disease/lymphoma. J Natl Compr Canc Netw 2008;6 (6):594-622.
Jost L. Hodgkin's disease: ESMO clinical recommendations for diagnosis, treatment and follow-
up. Ann Oncol 2007;18 (Suppl 2):ii53-4.
Kahl B, Byrd J, Flinn I, Wagner-Johnston N, Spurgeon S, al E. Significant Clinical Activity Of 
Cal-101, An Isoform-Selective Inhibitor Of Phosphatidylinositol 3 Kinase P110D, 
In Patients With Relapsed Or Refractory Indolent And Mantle Cell Lymphoma 
[Abstract 350] 11th Triennial International Conference on malignant Lymphoma 
(Icml). Lugano, Swizterland: 2011:
Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, et al. Therapeutic role of alemtuzumab 
(Campath-1H) in patients who have failed fludarabine: results of a large 
international study. Blood 2002;99 (10):3554-61.
Kuruvilla J. Standard therapy of advanced Hodgkin lymphoma. Hematology / the Education 
Program of the American Society of Hematology. American Society of 
Hematology 2009:497-506.
Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B, et al. Immunochemotherapy 
with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone 
significantly improves response and time to treatment failure, but not long-term 
outcome in patients with previously untreated mantle cell lymphoma: results of a 
prospective randomized trial of the German Low Grade Lymphoma Study Group 
(GLSG). J Clin Oncol 2005;23 (9):1984-92.
Moskowitz AJ, Perales MA, Kewalramani T, Yahalom J, Castro-Malaspina H, Zhang Z, et al. 
Outcomes for patients who fail high dose chemoradiotherapy and autologous stem 
cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J 
Haematol 2009;146 (2):158-63.
Okkenhaug K, Vanhaesebroeck B. PI3K-signalling in B- and T-cells: insights from gene-
targeted mice. Biochemical Society transactions 2003;31 (Pt 1):270-4.


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Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin 
prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic 
review and meta-analysis. Leuk Lymphoma 2009;50 (5):764-72.
Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, et al. Intensified 
chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab 
for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label 
randomised phase 3 trial. Lancet 2011;378 (9806):1858-67.
Salles GA. Clinical features, prognosis and treatment of follicular lymphoma. Hematology / the 
Education Program of the American Society of Hematology. American Society of 
Hematology 2007:216-25.
Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, et al. Long-term results of 
combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority 
of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol 1987;5 
(1):27-37.
Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T, et al. Immunochemotherapy with 
rituximab and overall survival in patients with indolent or mantle cell lymphoma: 
a systematic review and meta-analysis. J Natl Cancer Inst 2007;99 (9):706-14.
Surveillance Epidemiology and End Results (SEER) Program. SEER Stat Fact Sheets: Chronic 
Lymphocytic Leukemia. Available at: 
http://seer.cancer.gov/statfacts/html/clyl.html. Accessed 12 May 2011.
Vanhaesebroeck B, Ali K, Bilancio A, Geering B, Foukas LC. Signalling by PI3K isoforms: 
insights from gene-targeted mice. Trends Biochem Sci 2005;30 (4):194-204.
Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, et al. Ofatumumab 
as single-agent CD20 immunotherapy in fludarabine-refractory chronic 
lymphocytic leukemia. J Clin Oncol 2010;28 (10):1749-55.
Williams ME, Dreyling M, Winter J, Muneer S, Leonard JP. Management of mantle cell 
lymphoma: key challenges and next steps. Clinical lymphoma, myeloma & 
leukemia 2010;10 (5):336-46.
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Hodgkin's lymphomas. J Natl Compr Canc Netw 2011;9 (5):484-560.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


Idelalisib 
Protocol GS-US-313-2120 
Gilead Sciences, Inc. 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
199 EAST BLAINE STREET 
SEATTLE, WA 98102 
STUDY ACKNOWLEDGEMENT 
Final 
Amendment 2 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects Previously Treated with the 
Investigational PI3K¢ Inhibitor, GS-9820 
Amendment 2 26 August 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
po-----------------
Mario Marcondes, MD 
Gilead Medica] Monitor 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including a1l appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. l will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 56 
26 August 2016 


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Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a) Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause.  In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b) Definition of Male Fertility
For the purposes of this study, a male born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Idelalisib has insufficient data to exclude the possibility of a clinically relevant interaction with 
hormonal contraception that results in reduced contraception efficacy.  Therefore, contraceptive 
steroids are not recommended as a contraceptive method either solely or as a part of a 
contraceptive regimen.  Data from clinical pharmacokinetic interaction studies of idelalisib have 
demonstrated no adverse effect on fertility or embryo-fetal development.  However, there is no 
clinical data of idelalisib in pregnant women.  Please refer to the latest version of the 
investigator’s brochure for additional information. 
b) Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires using a highly effective 
contraceptive measure.  They must also not rely on hormone-containing contraceptives as a form 
of birth control during the study.  They must have a negative serum pregnancy test at Screening 
and a negative pregnancy test on the Baseline/Day 1 visit prior to randomization.  At minimum, a 
pregnancy test will be performed at the end of relevant systemic exposure.  In the event of a 
delayed menstrual period (over one month between menstruations), a pregnancy test must be 
performed to rule out pregnancy.  This is even true for women of childbearing potential with 
infrequent or irregular periods.  They must also agree to one of the following from Screening 
until 30 days after the end of relevant systemic exposure.


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Complete abstinence from intercourse of reproductive potential.  Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual lifestyle.
Or
Consistent and correct use of 1 of the following methods of birth control listed below. 

Intrauterine device (IUD) with a failure rate of <1% per year

Tubal sterilization

Ensure micro-insert system (provided confirmation of success 3 months after procedure)

Vasectomy in the male partner (provided that the partner is the sole sexual partner and had 
confirmation of surgical success 3 months after procedure)

Barrier methods (one female barrier and one male barrier must be used in combination)
Female barriers: Diaphragm with spermicide or Cervical cap with spermicide
Male barriers: Male condom (with or without spermicide)
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 30 days after the end of relevant systemic exposure
3) Contraception Requirements for Male Subjects
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment until the end of relevant 
systemic exposure.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM).  Female condom and male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last idelalisib dose. Subjects who become 
pregnant or who suspect that they are pregnant during the study must report the information to 
the investigator and discontinue idelalisib immediately. Subjects whose partner has become 
pregnant or suspects she is pregnant during the study must report the information to the 
investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome 
are outlined in Section 7.6.2.1.

Prot_001.pdf: 
Study Title: 
Sponsor: 
INDNumber: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Director 
or Clinical Program 
Manager: 
Gilead Medical 
Monitor: 
~ GILEAU 
CLINICAL STUDY PROTOCOL 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Ko Inhibitor, GS-9820 
Gilead Sciences, Inc. 
199 East Blaine Street 
Seattle, WA 98102 
N/A 
2015-005766-39 
Lymphoid Malignancies 
GS-US-313-2120 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
PO 
t-'t-'U 
PPD 
Mario Marcondes 
PPD 
PPD 
Protocol Version/Date: 
Original: 05 Januaty 2016 
Amendment 1 : 28 March 2016 
CONFIDENTIALITY STATEMENT 
The infmmation contained in this document, pruiicularly unpublished data, is the propetiy or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The infonnation is only to be used by you in 
connection with authorized clinical studies of the investigational dmg described in the protocol. 
You will not disclose any of the infmmation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessaty to obtain infmmed consent from those 
persons to whom the dmg may be administered. 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF IN-TEXT FIGURES ......................................................................................................................................4
PROTOCOL SYNOPSIS ..............................................................................................................................................5
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS......................................................................8
1.
INTRODUCTION ................................................................................................................................................9
1.1.
Background ..............................................................................................................................................9
1.2.
Idelalisib...................................................................................................................................................9
1.3.
Rationale for This Study ........................................................................................................................10
1.4.
Benefit/Risk Assessment for the Study..................................................................................................10
1.5.
Compliance ............................................................................................................................................10
2.
OBJECTIVES.....................................................................................................................................................11
3.
STUDY DESIGN................................................................................................................................................12
3.1.
Endpoints ...............................................................................................................................................12
3.2.
Study Design..........................................................................................................................................12
3.3.
Study Treatments ...................................................................................................................................12
3.4.
Duration of Treatment............................................................................................................................12
3.5.
Discontinuation Criteria.........................................................................................................................12
3.6.
Source Data............................................................................................................................................12
3.7.
Biomarker Testing..................................................................................................................................13
4.
SUBJECT POPULATION..................................................................................................................................14
4.1.
Number of Subjects and Subject Selection ............................................................................................14
4.2.
Inclusion Criteria....................................................................................................................................14
4.3.
Exclusion Criteria...................................................................................................................................14
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................16
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................16
5.2.
Description and Handling of Study Treatments .....................................................................................16
5.2.1.
Formulation..........................................................................................................................16
5.2.2.
Packaging and Labeling .......................................................................................................16
5.2.3.
Storage and Handling...........................................................................................................16
5.2.4.
Dosage and Administration of Idelalisib..............................................................................17
5.2.5.
Dispensing............................................................................................................................17
5.2.6.
Premedication.......................................................................................................................17
5.2.7.
Administration Instructions..................................................................................................17
5.2.8.
Dosing Schedule...................................................................................................................17
5.2.9.
Dose Levels..........................................................................................................................18
5.2.10.
Idelalisib Dose Adjustments.................................................................................................18
5.3.
Prior and Concomitant Medications.......................................................................................................21
5.3.1.
Anticancer or Experimental Therapies Other than Investigational 
Treatments............................................................................................................................21
5.3.2.
Antibiotics/ PJP Prophylaxis................................................................................................21
5.3.3.
Antidiarrheals.......................................................................................................................22
5.3.4.
Corticosteroids .....................................................................................................................23
5.3.5.
Granulocyte Colony-Stimulating Factors and Erythropoietin..............................................23
5.3.6.
Drugs that Alter CYP3A-Dependent Metabolism................................................................23


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5.3.7.
Drugs that undergo CYP3A-Dependent Metabolism...........................................................23
5.3.8.
Immunization .......................................................................................................................23
5.3.9.
Ultraviolet Exposure ............................................................................................................24
5.3.10.
Surgery .................................................................................................................................24
5.4.
Accountability for Idelalisib...................................................................................................................24
5.4.1.
Overdose Precautions...........................................................................................................25
5.4.2.
Inadvertent Exposure and Spill Precautions.........................................................................25
5.4.3.
Investigational Medicinal Product Return or Disposal.........................................................25
5.5.
Discontinuation from Study ...................................................................................................................25
6.
STUDY PROCEDURES ....................................................................................................................................27
6.1.
Subject Enrollment.................................................................................................................................27
6.1.1.
Subject Recruitment .............................................................................................................27
6.1.2.
Subject Compensation for Participation...............................................................................27
6.1.3.
Screening Visit .....................................................................................................................27
6.2.
Treatment Assessments..........................................................................................................................27
6.2.1.
Clinical Evaluation...............................................................................................................28
6.2.2.
Laboratory Assessments.......................................................................................................28
6.3.
End of Study...........................................................................................................................................29
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................33
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................33
7.1.1.
Adverse Events.....................................................................................................................33
7.1.2.
Serious Adverse Events........................................................................................................33
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................34
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................34
7.2.1.
Assessment of Causality for Idelalisib and Procedures........................................................34
7.2.2.
Assessment of Severity ........................................................................................................35
7.3.
Recommendations for Evaluation, Intervention, and Drug Discontinuation for Specific 
Adverse Events or Conditions................................................................................................................36
7.3.1.
Dermatological Events (Idelalisib).......................................................................................36
7.3.2.
Gastrointestinal Events.........................................................................................................36
7.3.3.
Hepatic Events......................................................................................................................38
7.3.4.
Hematological and Immunological Events...........................................................................38
7.3.5.
Pulmonary Events ................................................................................................................39
7.3.6.
Secondary Malignancies.......................................................................................................39
7.3.7.
Tumor Lysis Syndrome........................................................................................................39
7.4.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................40
7.4.1.
Serious Adverse Event (eSAE) Reporting Process ..............................................................40
7.5.
Gilead Reporting Requirements.............................................................................................................41
7.5.1.
Reporting of Adverse Events Relating and Other Anticipated Medical 
Events in the Study Population ............................................................................................41
7.5.2.
Toxicity Management...........................................................................................................42
7.6.
Special Situations Reports......................................................................................................................42
7.6.1.
Definitions of Special Situations..........................................................................................42
7.6.2.
Instructions for Reporting Special Situations.......................................................................42
8.
STATISTICAL CONSIDERATIONS................................................................................................................44
8.1.
Analysis Objectives................................................................................................................................44
8.2.
Safety Endpoints ....................................................................................................................................44
8.3.
Analysis Sets..........................................................................................................................................44
8.4.
Analysis Methods...................................................................................................................................44


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8.5.
Adverse Events.......................................................................................................................................44
9.
RESPONSIBILITIES..........................................................................................................................................45
9.1.
Investigator Responsibilities ..................................................................................................................45
9.1.1.
Good Clinical Practice..........................................................................................................45
9.1.2.
Independent Ethics Committee (IEC) Review and Approval...............................................45
9.1.3.
Informed Consent.................................................................................................................45
9.1.4.
Confidentiality......................................................................................................................46
9.1.5.
Study Files and Retention of Records ..................................................................................46
9.1.6.
Case Report Forms...............................................................................................................47
9.1.7.
Drug Accountability and Return ..........................................................................................48
9.1.8.
Inspections............................................................................................................................48
9.1.9.
Protocol Compliance............................................................................................................48
9.2.
Sponsor Responsibilities ........................................................................................................................48
9.2.1.
Protocol Modifications.........................................................................................................48
9.2.2.
Communications with Regulatory Authorities.....................................................................49
9.2.3.
Study Report and Publications .............................................................................................49
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................49
9.3.1.
Payment Reporting...............................................................................................................49
9.3.2.
Access to Information for Monitoring..................................................................................50
9.3.3.
Access to Information for Auditing or Inspections ..............................................................50
9.3.4.
Study Discontinuation..........................................................................................................50
10.
REFERENCES ...................................................................................................................................................51
11.
APPENDICES ....................................................................................................................................................54
Appendix 1.
Investigator Signature Page....................................................................................................55
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................56
LIST OF IN-TEXT TABLES
Table 5-1.
Idelalisib Dose Levels ............................................................................................................18
Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}.....................................................19
Table 6-1.
Schedule of Study Procedures................................................................................................31
Table 7-1.
Grading of Adverse Event Severity........................................................................................35
LIST OF IN-TEXT FIGURES
Figure 7-1.
Kaplan-Meier Time to Diarrhea or Colitis .............................................................................37


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
199 East Blaine Street
Seattle, WA 98102
Study Title: 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Kδ Inhibitor, GS-9820
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
Not Applicable
2015-005766-39
Study Centers 
Planned:
2 centers in the Netherlands
Objectives:
The primary objective of this study is as follows:

To provide open-label idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure who have had
objective evidence of clinical benefit defined as at least stable 
disease on imaging assessed by an independent review committee 
(IRC) and no toxicities prior to enrollment in this study that 
would preclude initiating therapy with idelalisib. Idelalisib and 
GS-9820 are both in the class of agents that inhibit PI3Kδ and as 
such this exchange of class for class agent is warranted and 
acceptable.
Study Design:
This study is an open-label, rollover study to provide idelalisib to 
subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure.
Number of Subjects 
Planned:
Approximately 6 subjects
Target Population:
Subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure who have objective evidence of clinical benefit defined 
as at least stable disease on imaging assessed by the IRC at final 
response assessment prior to enrollment in this study.
Duration of 
Treatment:
Subjects will be treated until progressive disease or intolerable 
toxicity.


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Diagnosis and Main 
Eligibility Criteria:
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be 
eligible for participation in this study:
1) Receiving GS-9820 in Study GS-US-315-0102 with objective 
evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC at the time of 
Study GS-US-315-0102 closure
2) For female subjects of childbearing potential, willingness to use a 
protocol recommended method of contraception during 
heterosexual intercourse from the signing of informed consent 
throughout the study treatment period and up to 30 days from the 
last dose of idelalisib (see Appendix 2)
3) For male subjects of reproductive potential having intercourse 
with females of childbearing potential, willing to use a protocol 
recommended method of contraception during heterosexual 
intercourse and to refrain from sperm donation throughout the 
study treatment period and for 90 days following discontinuation 
of idelalisib (see Appendix 2)
4) Willingness to comply with scheduled visits, drug administration 
plan, imaging studies, laboratory tests, other study procedures, 
and study restrictions, including mandatory prophylaxis for 
Pneumocystis jirovecii pneumonia (PJP). Note: Psychological, 
social, familial, or geographical factors that might preclude 
adequate study participation should be considered.
5) Evidence of a personally signed informed consent indicating that 
the subject is aware of the neoplastic nature of their disease and 
has been informed of the procedures to be followed, the 
experimental nature of the therapy, alternatives, potential benefits, 
possible side effects, potential risks and discomforts, and other 
pertinent aspects of study participation.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not
eligible to be enrolled in this study:
1) Known hypersensitivity or intolerance to any of the active 
substances or excipients in the formulation of idelalisib.
2) Toxicities that would preclude initiating therapy with idelalisib 
prior to enrollment (eg, history of drug-induced pneumonitis, 
ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding
5) Ongoing infection, treatment, or prophylaxis for CMV within the 
past 28 days.


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Study Procedures/
Frequency:
All subjects will receive idelalisib 150 mg taken orally, twice per day 
(BID) continuously. Subjects will undergo disease assessments and 
receive medical care per institutional standards of care.
Test Product, Dose, 
and Mode of 
Administration:
Idelalisib: 150 mg taken orally BID starting on Day 1 and 
administered continuously thereafter.
Reference Therapy, 
Dose, and Mode of 
Administration:
None
Criteria for 
Evaluation:
Safety:
Overall safety profile characterized by the type, frequency, severity, 
timing of onset, duration, and relationship to study therapy of ≥Grade 
3 adverse events (AEs), serious adverse events (SAEs), and deaths.
Efficacy:
Investigator response assessments
Statistical Methods:
Safety will be assessed by incidence of ≥ Grade 3 AEs, SAEs, and 
deaths. Efficacy will be evaluated by investigator response 
assessments. Both safety and efficacy will be assessed using data 
collected from subjects who received at least 1 dose of idelalisib. All 
analyses will be limited to descriptive summaries and listings.
Sample Size:
Up to 6 subjects
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
-HCG
beta human chorionic gonadotropin
BID
bis in die (twice daily)
CFR
Code of Federal Regulations
CLL
chronic lymphocytic leukemia
CRO
contract research organization
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DSPH
Drug Safety and Public Health
eCRF
electronic case report form
EOS
end of study
EU
European Union
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
G-CSF
granulocyte colony-stimulating factor
GCP
good clinical practice
GM-CSF
granulocyte-macrophage colony-stimulating factors
HLT
High-Level Term
HMG-CoA
3-hydroxy-3-methyl-glutaryl-Coenzyme A
IB
investigator’s brochure
ICH
International Conference on Harmonisation
iNHL
indolent non-Hodgkin lymphoma
IEC
independent ethics committee
IUD
intrauterine device
MCL
mantle cell lymphoma
NHL
non-Hodgkin lymphoma
PI3K
phosphatidylinositol 3-kinase
PDE5
phosphodiesterase-5
PJP
pneumocystis jirovecii pneumonia
SAE
serious adverse event
SOC
system organ class
SOP
standard operating procedure
SADR
serious adverse drug reaction
SUSAR
suspected unexpected serious adverse reactions
ULN
upper limit of normal


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1.
INTRODUCTION
1.1.
Background
B-cell lymphoid malignancies comprise the most common hematological malignancies 
{Surveillance Epidemiology and End Results (SEER) Program 2011}. These cancers arise from 
the accumulation of monoclonal B lymphocytes in lymph nodes and often in organs such as 
blood, bone marrow, lymph nodes, spleen, and liver. Among the variants of these cancers are 
non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), indolent 
non Hodgkin lymphoma (iNHL), and mantle cell lymphoma (MCL), as well as chronic 
lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL). These disorders are characterized 
by lymphadenopathy that is frequently disturbing for patients and can sometimes induce life 
threatening organ dysfunction; patients may also have constitutional symptoms (fevers, night 
sweats, and/or weight loss) and fatigue {Diehl et al 2004}, {Salles 2007}, {Dighiero et al 2008}, 
{Williams et al 2010}. 
The goal of therapy for these diseases is to induce tumor regression and delay tumor progression 
in order to control disease-related complications and potentially extend life. Patients who require 
treatment are commonly given chemotherapeutic and/or immunotherapeutic agents {Hoppe et al 
2008}, {Jost 2007} {Eichhorst et al 2010}, {Friedberg 2011}, {Gribben et al 2011}, {Zelenetz et 
al 2011}. Among patients with iNHL, CLL, and MCL, front line combination therapies can be 
effective in providing durable remissions {Lenz et al 2005}, {Santoro et al 1987}, {Schulz et al 
2007}, {Hallek et al 2010}, {Recher et al 2011}. In DLBCL and HL, such front-line regimens 
can be curative in the majority of patients {Santoro et al 1987}, {Kuruvilla 2009}, {Recher et al 
2011}. However, most treated patients with iNHL, CLL, and MCL will eventually experience 
disease relapse. Some patients with DLBCL or HL will experience recurrent disease even with 
initial induction therapy and later salvage therapy. For any of these cancers, further sequential 
therapies are given in an attempt to control disease manifestations. Despite use of agents with 
differing mechanisms of action, progressive resistance to treatment develops. Patients with 
progressive disease have a poor prognosis; median survival for these groups of patients is 
generally ≤2 years {Keating et al 2002}, {Goy et al 2009}, {Hess et al 2009}, {Moskowitz et al 
2009}, {Di Bella et al 2010}, {Wierda et al 2010}, {Friedberg 2011}. Novel mechanisms of 
action are needed to offer additional treatment options for patients with lymphoid malignancies 
who are experiencing progressive lymphadenopathy or symptoms due to disease progression.
1.2.
Idelalisib
Idelalisib (Zydelig®) was first approved in the United States on July 23, 2014 for the treatment 
of relapsed CLL, follicular lymphoma (FL), and small lymphocytic lymphoma (SLL), followed 
by approval in the EU on September 18, 2014 (centrally authorized). To date, Zydelig is 
currently approved in 37 countries. Refer to local labeling for the approved indication 
statements.
Idelalisib is a potent competitive inhibitor of the adenosine triphosphate (ATP) binding site of 
the phosphatidylinositol 3 kinase (PI3K) p110δ catalytic domain, which has been shown to be 


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prominently expressed in cells of hematopoietic origin {Okkenhaug et al 2003}, 
{Vanhaesebroeck et al 2005}. The effects of p110δ on lymphocyte activation/function, cellular 
proliferation, and protection from apoptosis provide the rationale for targeting this isoform as a 
therapy for hematologic malignancies.
Further details on the preclinical pharmacology, toxicology, metabolism and pharmacokinetics 
(PK) of idelalisib can be found in the idelalisib Investigator’s Brochure (IB).
1.3.
Rationale for This Study
Study GS-US-315-0102 is being conducted to evaluate the safety and efficacy of GS-9820, a 
second generation PI3Kδ inhibitor in subjects with iNHL, DLBCL, MCL, HL, or CLL. GS-9820 
was anticipated to offer similar efficacy to idelalisib in lymphoid malignancies while offering a 
more favorable safety profile than idelalisib. The development of GS-9820 has been 
discontinued by Gilead Sciences due to demonstration of a similar safety profile to idelalisib. 
Manufacture of the investigational agent GS-9820 has been discontinued, and will no longer be 
available to the ongoing subjects in Study GS-US-315-0102.  
This rollover study provides access to idelalisib for eligible subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure who have had objective evidence of clinical 
benefit defined as at least stable disease on imaging assessed by the independent review 
committee (IRC) and no toxicities prior to enrollment in this study that would preclude initiating 
therapy with idelalisib.  Subjects will be allowed to receive treatment on this study until 
unacceptable toxicity, progressive disease, study withdrawal, or death occurs.
1.4.
Benefit/Risk Assessment for the Study
Subjects enrolled in this study have a serious life-threatening disease, with limited treatment 
options. Without treatment their disease will progress and ultimately be fatal. Transitioning 
subjects from GS-9820 to idelalisib, a similar agent in class that has shown proof of clinical 
activity and has received regulatory approval for the treatment of relapsed CLL and iNHL 
{Gilead Sciences Limited 2015}, is rational as described in Section 1.3 of this protocol; 
therefore, subjects enrolled in this study may derive clinical benefit defined as an improvement 
in disease control such as response to study treatment. The risks that may accompany study 
treatment are related to the identified and potential toxicities of treatment with idelalisib and are 
described in Section 5 of this protocol and in the ICF. The management of these toxicities is 
described in Table 5-2. Taken together, there is a positive benefit/risk for initiating study 
treatment with idelalisib in subjects previously treated with GS-9820.
1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To provide idelalisib, a marketed PI3Kδ inhibitor, in lieu of GS-9820, an investigational 
second generation PI3Kδ inhibitor, to subjects receiving GS-9820 in Study GS-US-315-0102
at the time of study closure who have had objective evidence of clinical benefit defined as at 
least stable disease on imaging assessed by the IRC and no toxicities prior to enrollment in 
this study that would preclude initiating therapy with idelalisib. Idelalisib and GS-9820 are 
both in the class of agents that inhibit PI3Kδ and as such this exchange of class for class 
agent is warranted and acceptable.


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3.
STUDY DESIGN
3.1.
Endpoints
There is no primary endpoint of this study.
3.2.
Study Design
This study is an open-label, rollover study to provide idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure.
3.3.
Study Treatments
All subjects will receive idelalisib 150 mg taken orally, twice per day (BID) continuously. 
3.4.
Duration of Treatment
Treatment will continue until unacceptable toxicity, disease progression, study discontinuation 
(outlined below), or death occurs.
3.5.
Discontinuation Criteria
A subject may be withdrawn from the study under the following circumstances:

The subject withdraws consent to participate in the study

The subject permanently discontinues idelalisib treatment for any reason

The subject experiences a toxicity that necessitates permanent discontinuation of idelalisib
treatment

The subject has progressive disease 

The subject does not comply with the requirements of the protocol (eg initiation of a 
non-protocol anti-tumor treatment)

Gilead, a regulatory agency, or an independent ethics committee (IEC) discontinues the study
The reason for withdrawal will be recorded in the eCRF.
3.6.
Source Data
Electronic data (ie, diagnostic machines that transcribe data directly to a database, or data entered 
directly into an Electronic Medical Record system) is considered source data, provided the data 
is not recorded directly on the CRF/eCRF, and provided there is a clear audit trail in the 


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electronic record(s). No data will be recorded directly on the CRF/eCRF, and any data recorded 
directly on the CRF/eCRF will not be considered source data.
3.7.
Biomarker Testing
There will be no biomarker testing in this study.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 6 subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure are anticipated.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1. Receiving GS-9820 in Study GS-US-315-0102 with objective evidence of clinical benefit 
defined as at least stable disease on imaging assessed by the IRC at the time of 
Study GS-US-315-0102 closure
2. For female subjects of childbearing potential, willingness to use a protocol recommended 
method of contraception during heterosexual intercourse from the signing of informed 
consent throughout the study treatment period and up to 30 days from the last dose of 
idelalisib (see Appendix 2)
3. For male subjects of reproductive potential having intercourse with females of childbearing 
potential, willing to use a protocol recommended method of contraception during 
heterosexual intercourse and to refrain from sperm donation throughout the study treatment 
period and for 90 days following discontinuation of idelalisib (see Appendix 2)
4. Willingness to comply with scheduled visits, drug administration plan, imaging studies, 
laboratory tests, other study procedures, and study restrictions, including mandatory 
prophylaxis for Pneumocystis jirovecii pneumonia (PJP). Note: Psychological, social, 
familial, or geographical factors that might preclude adequate study participation should be 
considered.
5. Evidence of a personally signed informed consent indicating that the subject is aware of the 
neoplastic nature  of their disease and has been informed of the procedures to be followed, 
the experimental nature of the therapy , alternatives, potential benefits, possible side effects, 
potential risks and discomforts, and other pertinent aspects of study participation.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not eligible to be enrolled in this 
study:
1) Known hypersensitivity or intolerance to any of the active substances or excipients in the 
formulation of idelalisib.


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2) Toxicities that would preclude initiating therapy with idelalisib prior to enrollment
(eg history of drug-induced pneumonitis, ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding.
5) Ongoing infection, treatment, or prophylaxis for CMV within the past 28 days.


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5. 
INVESTIGATIONAL MEDICINAL PRODUCTS 
5.1. 
Randomization, Blinding and Treatment Codes 
The study is open-label and non-randomized. 
5.2. 
Description and Handling of Study Treatments 
5.2.1. 
Formulation 
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Idelalisib 150 mg tablets are pink, oval-shaped and debossed with "GSI" on one side and 
"150" on the other. The 100 mg tablets are orange, oval-shaped and debossed with " GSI" on 
one side and ' ' 100'' on the other. All tablets ru·e film-coated, and include the following inactive 
exciQients: PD 
5.2.2. 
Packaging and Labeling 
Idelalisib tablets, 150 mg or 100 mg, are packaged in white, high density polyethylene (HDPE) 
bottles. Each bottle contains 60 tablets and polyester packing material. Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an induction-
sealed and aluminum-faced liner. 
Idelalisib to be distributed to centers in the US and other pruticipating countries shall be labeled 
to meet applicable requirements of the United States Food and Dmg Administration (FDA), EU 
Guideline to Good Manufactming Practice- Annex 13 (Investigational Medicinal Products), 
and/or other local regulations. 
5.2.3. 
Storage and Handling 
Idelalisib should be stored at controlled room temperatme of25°C (77°F); excmsions ru·e 
permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the 
label. Until dispensed to the subjects, all bottles of study mugs should be stored in a secmely 
locked ru·ea, accessible only to authorized site personnel. 
To ensme the stability and proper identification, study mug should not be stored in a container 
other than the container in which they were supplied. Consideration should be given to handling, 
preparation, and disposal tln·ough measmes that minimize m·ug contact with the body. 
Appropriate precautions should be followed to avoid direct eye contact or exposme when 
handling. 
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5.2.4.
Dosage and Administration of Idelalisib
Idelalisib formulated drug product of 100 and 150 mg strengths has been manufactured for 
clinical trials and will be provided to the subject to be taken at home. Subjects should be 
instructed to take the doses with water. Idelalisib may be taken with or without food. Missed 
doses should not be taken unless it is within 6 hours of the scheduled dosing and vomited doses 
should be retaken only if the tablet is visible in the vomitus.
Idelalisib will be taken twice daily. Idelalisib should be taken at approximately the same times 
each day. Ideally, doses should be taken at approximately 12 hour intervals as instructed 
(eg, at 7 AM and at 7 PM). While it is realized that variations in dosing schedule may occur in 
the outpatient setting, the prescribed regimen should be followed as closely as possible.
5.2.5.
Dispensing
The clinic staff (eg, pharmacist or other qualified person) will be responsible for dispensing 
idelalisib. It is planned that idelalisib will be dispensed at 4-week intervals through the 
first 16 weeks of treatment, at 8-weeks, and at 12-week intervals thereafter. Sufficient idelalisib
will be provided for each study period at the beginning of the period. Tablets should be 
dispensed in the original bottles provided.
The clinic staff (eg, pharmacist or other qualified person) will write the subject number on each 
bottle that is dispensed. Immediately before dispensing, the clinic staff will write the bottle 
number for each dispensed bottle in the idelalisib administration record corresponding to the 
subject number.
5.2.6.
Premedication
No specific pre-medications or supporting medications are required in conjunction with idelalisib
administration.
5.2.7.
Administration Instructions
The prescribed dose of idelalisib should be taken orally. At each dose administration, the tablet 
number corresponding to the appropriate dose of idelalisib is to be swallowed whole with 
100 to 200 mL (~4 to 8 ounces) of water. In case of breakage of the tablets in the oral cavity, 
additional water should be taken as a rinse.
Idelalisib may be taken with or without food. There are no known dietary restrictions related to 
idelalisib use.
5.2.8.
Dosing Schedule
Idelalisib will be administered on a BID schedule. Idelalisib should be taken at approximately 
the same times each day.


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5.2.9.
Dose Levels
Idelalisib dose levels are shown in Table 5-1. The starting dose level will be 150 mg BID. The 
lower dose level (Dose Level -1) is provided in case a subject requires a dose modification.
Table 5-1.
Idelalisib Dose Levels
Dose Level
Dosing Regimen
Starting
150 mg BID
-1
100 mg BID
Abbreviation: BID=twice per day
Consistent with Table 5-2, if a subject experiences an AE that is suspected to be related to 
idelalisib during the course of study, idelalisib administration may be held, as necessary, until the 
AE resolves or stabilizes to an acceptable degree (as defined in Table 5-2). Thereafter, idelalisib 
may be reinitiated at either the Starting Dose Level or at Dose Level -1 consistent with the 
instructions in Section 5.2.10. A further attempt at reinitiation of therapy at Dose Level -1 may 
be attempted if the investigator feels that a second rechallenge at that dose level is medically 
appropriate. If the subject cannot tolerate idelalisib after 2 rechallenges at Dose Level -1 for the 
same AE, then the subject should be discontinued from idelalisib treatment.
After an idelalisib dose reduction, the dose need not be re-escalated, even if there is minimal or 
no toxicity with the reduced dose. However, if the subject tolerates Dose Level -1 of idelalisib
for 4 weeks, then the dose may be increased back to Starting Dose Level, at the discretion of 
the investigator. Such a re-escalation may be particularly warranted if further evaluation reveals 
that the AE that led to the dose reduction was not related to idelalisib.
5.2.10.
Idelalisib Dose Adjustments
The dose adjustment recommendations in Table 5-2 are based on the Common Terminology 
Criteria for Adverse Events (CTCAE) grade of specific toxicities. However, exceptions are 
expected for subjects who initiate study treatment with low blood counts. Clinical judgment 
should apply, and in cases of uncertainty, the study medical monitor should be contacted.
The dose modification instructions focus on the types of events most commonly attributed to 
idelalisib. The recommendations provided in Table 5-2 comprise only guidelines; variations from 
these recommendations may be warranted based on an investigator’s individual judgment in 
considering potential risks, benefits, and therapeutic alternatives available to each subject.


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Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}
NCI CTCAE Gradea
Idelalisib
HEMATOLOGICAL ADVERSE EVENTS
Neutropenia
Grade 2 neutropenia
Maintain current dose level and schedule.
Grade 3 neutropenia
Maintain current dose level and schedule.  Blood counts should be monitored at least 
weekly.
Grade 4 neutropenia
(or occurrence of 
neutropenic fever or 
infection)
Delay idelalisib dosing.  
Blood counts should be monitored at least weekly until ANC ≥ 0.5 x 109/L, at which 
point idelalisib dosing may be resumed at 100 mg BID.
Neutropenia should be managed according to established clinical guidelines.
Thrombocytopenia
Grade 2
Maintain current dose level and schedule
Grade 3
Maintain current dose level and schedule.
Grade 4
During combination therapy period, maintain current dose level. During continuing 
therapy period, withhold for bruising or bleeding until Grade 3, May resume at same 
or reduced dose level at investigator discretion.
NON-HEMATOLOGICAL ADVERSE EVENT
Rash
Grade 1
Maintain current dose level and schedule
Grade 2
Maintain current dose level and schedule 
Grade 3
Withhold study drug until Grade 1. Resume at lower dose level or discontinue study 
drug at investigator discretion.
Grade 4
Withhold study drug until Grade 1. Resume at lower dose level or discontinue study 
drug at investigator discretion.
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
Any Grade
Discontinue idelalisib.
Institute systemic immunosuppression per institutional standards.
Gastrointestinal Inflammation/Diarrheab
Grade 1
Provide anti-diarrheal (eg, loperamide) and maintain current study drug dose level 
and schedule
Grade 2
Provide anti-diarrheal (eg, loperamide). Consider addition of anti-inflammatory agent 
(eg, sulfasalazine, budesonide). Maintain current study drug dose and schedule.
Grade 3
Withhold study drug.  Rule out infectious etiology including CMV. Consider anti-
diarrheal (eg, loperamide) and/or addition of anti-inflammatory agent (eg, 
sulfasalazine, budesonide). At Grade 1, may resume at lower dose level or 
discontinue study drug at investigator discretion.


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NCI CTCAE Gradea
Idelalisib
Grade 4
Withhold study drug.  Rule out infectious etiology including CMV. Consider anti-
diarrheal (eg, loperamide) and/or addition of anti-inflammatory agent (eg, 
sulfasalazine, budesonide). At Grade 1, may resume at lower dose level or 
discontinue study drug at investigator discretion. 
Hepatic Adverse Events (elevations in ALT, AST, or bilirubin)
Grade ≤1
(ALT/AST 3xULN)
(Bilirubin 1.5xULN)
Maintain current dose level and schedule.
Grade 2
(ALT/AST > 3-5xULN)
(Bilirubin > 1.5- 3xULN)
Maintain current
dose level and schedule. Monitor ALT, AST, ALP, and bilirubin at least 1x per week.
Grade 3
(ALT/AST>5-20xULN)
(Bilirubin > 3-10xULN)
Withhold study drug. Monitor ALT, AST, ALP, and bilirubin at least 1x per week 
until all abnormalities are Grade 1. If bilirubin abnormality is Grade <3 resume 
study drug at same dose level. If bilirubin abnormality is Grade 3, resume at lower 
dose level
Grade 4
(ALT/AST>20xULN)
(Bilirubin > 10xULN)
Withhold study drug. Monitor ALT, AST, ALP, and bilirubin at least 1x per week 
until all abnormalities are Grade 1. If bilirubin abnormality is Grade <4 resume 
study drug at lower dose level. If bilirubin abnormality is Grade 4, discontinue study 
drug.
Pneumonitis (dyspnea, cough, hypoxia without obvious infectious cause)
Grade 1
Withhold study drug until resolution to baseline. May resume at lower dose level or 
discontinue study drug at investigator discretion.
Grade 2
Withhold study drug and discontinue permanently.
Grade 3
Withhold study drug and discontinue permanently. Institute systemic corticosteroids
Grade 4
Withhold study drug and discontinue permanently. Institute systemic corticosteroids.
Pneumocystis pneumonia
Any Grade
Discontinue idelalisib
Unequivocal CMV infectionc
Any Grade
Discontinue idelalisib
Other Nonhematological Adverse Events
Grade 2
Maintain current dose level and schedule
Grade 3
Withhold study drug until Grade 1. May resume study drug at lower dose level or 
discontinue study drug at investigator discretion.
a
CTCAE, Version 4.03.
b
See Section 6.2. and 7.3.2. for additional requirements regarding an AE of diarrhea
c
CMV should be diagnosed using clinical or laboratory criteria per established institutional standard
Abbreviations: ALP=alkaline phosphatase, ALT=alanine aminotransferase, ANC=absolute neutrophil count, 
AST=aspartate aminotransferase, CTCAE=Common Terminology Criteria for Adverse Events, 
G-CSF=granulocyte-colony-stimulating factor, NCI=National Cancer Institute, ULN=upper limit of normal


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5.3.
Prior and Concomitant Medications
If considered necessary for the subject’s well-being, drugs for concomitant medical conditions or 
for symptom management may be given at the discretion of the investigator.
Any concomitant medications prescribed as a therapeutic intervention for or resulting in an AE 
or SAE during the course of the study and the reason for use should be recorded on the eCRFs.
5.3.1.
Anticancer or Experimental Therapies Other than Investigational 
Treatments
Except for corticosteroids, no other anticancer therapies (including chemotherapy, radiation, 
antibody therapy, immunotherapy, or other experimental therapies) of any kind are permitted. 
Subjects are not allowed to participate concurrently in any other therapeutic clinical study.
5.3.2.
Antibiotics/ PJP Prophylaxis
5.3.2.1.
Infectious Events
Patients with lymphoid cancers receiving idelalisib have developed serious and fatal infections 
during therapy. Opportunistic infections, most notably Pneumocystis jirovecii pneumonia (PJP) 
and CMV infection, have most frequently occurred within the first 6 months of treatment with 
idelalisib and are increased in the context of concurrent myelosuppressive therapy such as 
bendamustine.
Subjects must receive trimethoprim-sulfamethoxazole or other established prophylaxis for PJP
throughout the course of idelalisib treatment.  Prophylaxis will continue until the CD4+ T-cell 
count is documented to be >200 cells/mcL after idelalisib treatment ends. Subjects must 
permanently discontinue idelalisib upon diagnosis of PJP.
CMV surveillance for active disease (quantitative PCR or PP65 antigen) must be conducted 
approximately every 4 weeks throughout the course of idelalisib treatment. CMV viral load 
testing should be performed from the same specimen type whenever possible and caution should 
be exercised when comparing CMV viral load results across different testing centers. If 
unequivocal clinical or laboratory evidence of CMV infection is present, the subject must 
permanently discontinue idelalisib treatment and undergo effective antiviral treatment according 
to established clinical guidelines.
In high-risk subjects (history of recurrent infection, allogeneic transplant, treatment with 
alemtuzumab, hypogammaglobulinemia) other infection prophylaxis should be considered per 
consensus guidelines. Administration of intravenous immunoglobulin is permitted per standard 
institutional practice {Raanani et al 2009}. For subjects who develop an infection, appropriate 
medical therapy should be instituted in a timely manner.
Trimethoprim sulfamethoxazole is rated a Pregnancy category C agent. In rats, oral doses of 
533 mg/kg or 200 mg/kg produced teratologic effects manifested mainly as cleft palates. One 


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survey found no congenital abnormalities in 35 children whose mothers had received oral
sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter. Because 
sulfamethoxazole and trimethoprim may interfere with folic acid metabolism it should be used 
during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Dapsone is rated a Pregnancy Category C agent.  Extensive, but uncontrolled experience and two 
published surveys on the use of Dapsone in pregnant women have not shown that Dapsone 
increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can 
affect reproduction capacity. Because of the lack of animal studies or controlled human 
experience, Dapsone should be given to a pregnant woman only if clearly needed. Dapsone is 
excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates. 
Because of the potential for tumorgenicity shown for Dapsone in animal studies a decision 
should be made whether to discontinue nursing or discontinue the drug taking into account the 
importance of drug to the mother.
Atovaquone is rated a Pregnancy Category C agent.  Atovaquone is teratogenic and did not cause 
reproductive toxicity in rats at plasma concentrations up to 2 to 3 times the estimated human 
exposure. Atovaquone can cause maternal toxicity in rabbits at plasma concentrations that were 
approximately one half the estimated human exposure. Mean fetal body lengths and weights 
were decreased and there were higher numbers of early resorption and post-implantation loss per 
dam. It is not clear whether these effects are caused by atovaquone directly or are secondary to 
maternal toxicity. Concentrations of atovaquone in rabbit fetuses averaged 30% of the concurrent 
maternal plasma concentrations.  There are no adequate and well-controlled studies in pregnant 
women. Atovaquone should be used during pregnancy only if the potential benefit justifies the 
potential risk to the fetus. It is not known whether atovaquone is excreted into human milk. 
Because many drugs are excreted into human milk, caution should be exercised when 
Atovaquone is administered to a nursing woman. In a rat study, atovaquone concentrations in the 
milk were 30% of the concurrent atovaquone concentrations in the maternal plasma.
Aerosolized Pentamidine (NebuPent) is a Pregnancy Category C agent.  There are no adequate 
and well controlled studies of NebuPent in pregnant women. One literature report indicated that 
intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; 
teratogenicity was not observed in this study. It is unknown whether pentamidine administered 
via the aerosolized route crosses the placenta at clinically significant concentrations. It is not 
known whether NebuPent can cause fetal harm when administered to a pregnant woman. 
NebuPent should be given to a pregnant woman only if clearly needed.  It is not known whether 
NebuPent is excreted in human milk.  NebuPent should not be given to a nursing mother unless 
the potential benefits are judged to outweigh the unknown risks.
5.3.3.
Antidiarrheals
As needed, subjects may be prescribed loperamide (Imodium® or others) or diphenoxylate and 
atropine (Lomotil®) to control diarrheal symptoms.


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5.3.4. 
Corticosteroids 
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Subjects may receive topical, inhaled, enteric, or systemic corticosteroids while on study. 
5.3.5. 
Granulocyte Colony-Stimulating Factors and Erythropoietin 
Granulocyte-macrophage colony-stimulating factor (GM-CSF) should not be administered given 
the potential for GM-CSF-related inflammatory symptoms. 
G-CSF (filgrastim, PEG-filgrastim, lenograstim) may be administered in response to 
Grade 4 neutropenia or neutropenic complications; (see Table 5-2). 
While erythropoietic agents (eg, erythropoietin or darbepoetin) may be administered for 
Grade ~3 anemia, their use in this study is discouraged given the potential to confound 
assessments of improvements in bone marrow function related to idelalisib. 
5.3.6. 
Drugs that Alter CYP3A-Dependent Metabolism 
Idelalisib is metabolized to its major metabolite PO 
via aldehyde oxidase and 
cytochrome P450 3A (CYP3A). Idelalisib also undergoes minor metabolism by UDP 
glucoronosyltransferase 1-4 (UGT1A4). The AUC of idelalisib was increased 1.8 fold when 
idelalisib was coadministered with a strong CYP3A inhibitor. Therefore, if subjects are taking 
concomitant strong CYP3A inhibitors, the subject should be monitored closely for signs of 
idelalisib toxicity and the dose modifications for adverse reactions should be followed in the 
event of toxicity (see Table 5-2). 
Additionally, idelalisib exposures are approximately 75% lower when coadministered with 
rifampin, a highly potent inducer of CYP3A. Therefore, avoid coadministration of strong 
inducers ofCYP3A (rifampin, carbamazepine, phenytoin, and St. John's wort) with idelalisib. 
5.3.7. 
Drugs that undergo CYP3A-Dependent Metabolism 
The major metabolite of idelalisib, PO 
, is a reversible and time dependent inhibitor of 
CYP3A; accordingly, coadministration of idelalisib with midazolam, a probe CYP3A substrate, 
resulted in a ~5-fold increase in midazolam systemic exposure (AUC). Coadministration of 
drugs that are narrow therapeutic index CYP3A substrates with idelalisib may result in an 
increase in their systemic exposures ( eg, antiarrhythmics, calcium channel blockers, 
benzodiazepines, certain HMG-CoA reductase inhibitors, phosphodiesterase-S [PDE5] 
inhibitors, warfarin). Avoid coadministration of drugs that are narrow therapeutic index CYP3A 
substrates ( eg, alfentanil, cyclosporine, sirolimus, tacrolimus, cisapride, pimozide, fentanyl, 
quinidine, ergotamine, dihydroergotamine, astemizole, terfenadine) with idelalisib. 
5.3.8. 
Immunization 
Because of its actions to inhibit PI3K8-dependent B-cell function, high doses of idelalisib can 
impair primary or secondary responses to immunization in animals. 
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The specific clinical relevance of these findings with idelalisib is unknown. However, for 
subjects who are at substantial risk of an infection (eg, influenza) that might be prevented by 
immunization, consideration should be given to providing the vaccine prior to initiation of study 
therapy.
Of note, the safety of immunization with live viral vaccines following idelalisib therapy has not 
been studied and vaccination with live virus vaccines during study treatment is not 
recommended.
5.3.9.
Ultraviolet Exposure
While nonclinical findings suggest the hypothetical potential for phototoxicity in humans, 
available clinical data do not reveal a photosafety concern. Although specific clinical correlates 
for these nonclinical data are not available, investigators and study subjects should be observant 
for the possibility that study participants may have exaggerated sunburn reactions (eg, burning,
erythema, exudation, vesicles, blistering, edema) involving areas of skin exposed to ultraviolet 
light.
5.3.10.
Surgery
There are no known effects of idelalisib on coagulation or wound healing. Pending receipt of 
additional information and considering the subject’s current platelet counts, idelalisib may be 
continued in the peri-procedural period in subjects who require surgery or invasive procedures.
5.4.
Accountability for Idelalisib
The disposition of all idelalisib should be documented from the time of receipt at the site through 
subject dispensing and return.
Study personnel must ensure that idelalisib is kept in a secure locked area with access limited to 
authorized personnel. The idelalisib must not be used outside the context of this protocol. Under 
no circumstances should the investigator or site personnel supply idelalisib to other investigators 
or clinics, or allow the idelalisib to be used other than as directed by this protocol.
The investigator and/or the responsible site personnel must maintain accurate records of the 
receipt of idelalisib shipped by Gilead Sciences or its designee, including, but not limited to, the 
date received, lot number, amount received, and the disposition of all idelalisib. Upon receipt of 
a drug shipment, the shipment must be logged into the idelalisib accountability records, these 
records must also be maintained to include the subject number to whom the idelalisib was 
dispensed and the date, quantity and lot number of the idelalisib dispensed.
Depending upon the decision of Gilead Sciences, remaining unused idelalisib supply will be 
returned to Gilead Sciences or its designee after the study is completed or will be discarded or 
destroyed at the clinical site. If the idelalisib is discarded or destroyed at the clinical site, 
standard institutional policy should be followed. Records documenting the date of idelalisib
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5.4.1.
Overdose Precautions
In Phase 1 studies, an MTD for idelalisib was not reached when administering the drug 
continuously at dose levels of 350 mg/dose BID (700 mg per day) {Coutre et al 2011}, {Kahl et 
al 2011}. However, in this protocol, an overdose is defined as administration of more than the 
prescribed daily dose (ie, >300 mg in a single day).
The Gilead Sciences medical monitor should be contacted if an idelalisib overdose occurs. Cases 
of idelalisib overdose will result in specific reporting requirements.
5.4.2.
Inadvertent Exposure and Spill Precautions
Based on available data from nonclinical studies, idelalisib does not appear to be acutely toxic, 
genotoxic, or irritative at levels that are likely to result from inadvertent exposure to the contents 
of broken tablets. However, personnel handling the drug should use reasonable precautions to 
avoid eye contact, skin contact, inhalation, or ingestion of the idelalisib product. For further 
information regarding inadvertent exposure and spill precautions, please consult the idelalisib
investigator brochure.
5.4.3.
Investigational Medicinal Product Return or Disposal
Subjects will be instructed to return any unused idelalisib in the original container at post 
treatment study visits. Returned medication will be reconciled by the investigator in order to 
monitor the subject’s compliance with the medication regimen. When possible, all idelalisib
returned by the subject should be retained for review by the study site monitor prior to return to 
Gilead Sciences or destruction.
5.5.
Discontinuation from Study
Subject study participation may be ended due to any of the follow reasons:

Withdrawal of consent

Objective evidence of disease progression.

Unacceptable toxicity or unable to tolerate a second rechallenge for the same AE.

Any subject who becomes pregnant or begins breastfeeding.

Initiation of non-protocol specfied anticancer therapy.

Noncompliance with idelalisib administration, study procedures, or study requirements.

The investigator may discontinue idelalisib, if it is not in the subject’s best interest to 
continue.

Any subject who is lost to follow-up.


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
Death

Discontinuation of study by the Sponsor, a regulatory agency, or an EC


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Table 6-1 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment 
6.1.1.
Subject Recruitment
This study will enroll subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure who have had objective evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC and no toxicities prior to enrollment in this study that would
preclude initiating therapy with idelalisib. The study sponsor will post a description of the study 
on the ClinicalTrials.gov website.
6.1.2.
Subject Compensation for Participation
Subjects will not be paid for participation in the study other than medical care that may be 
provided. Payments for such items as lost wages, disability, discomfort due to injury, or meals 
obtained while waiting at the clinical research center will not be provided. Through the informed 
consent process, study candidates will be notified that their insurance company could be charged 
for standard care that is a component of this research study and that subjects may be responsible 
for co-payments and deductible payments that are typical for their insurance coverage.
6.1.3.
Screening Visit
The investigator must inform each prospective subject of the nature of the study, explain the 
potential risks, and obtain written informed consent from the subject and/or a legal guardian 
prior to performing any study-related screening procedures. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (CRF/eCRF).  
All other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history CRF/eCRF.  
See Section 7 Adverse Events and Toxicity Management for additional details.
6.2.
Treatment Assessments
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all SAEs, as well as any non-serious all grade AEs on the AE case 
report form (eCRF). All other untoward medical occurrences observed during the screening 


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period, including exacerbation or changes in pre-existing conditions are considered medical 
history (not collected for this study). See Adverse Events and Toxicity Management (Section 7) 
for additional details.
While on study, the subject will return at regular intervals for the following procedures:

Evaluation of disease status per standard of care

Laboratory lab tests as outlined under Section 6.2.2. 

Recording of all grade AEs and all SAEs
— For an AE of Diarrhea or Colitis:
1. Obtain history of onset and duration of diarrhea, including description of number of 
stools and stool composition (eg, watery, bloody, nocturnal), travel history, dietary 
changes and a medication review to identify possible diarrheogenic agents
2. Perform physical examination including assessment for fever, dizziness, abdominal 
pain/cramping, and weakness (ie, evaluate for sepsis, bowel obstruction, dehydration)

Return of used drug supplies and dispensing of new idelalisib supply
The specific study procedures to be conducted for each subject enrolled in the study are 
presented in Table 6-1 and are described in the sections that follow.
6.2.1.
Clinical Evaluation
While on study, the subject will be followed for disease status according to standard of care. At 
each study visit the subject’s disease status will be assessed. If no change in disease status is 
identified and the subject is dispensed additional idelalisib, the most recent prior response 
documented for the study will be recorded.
6.2.2.
Laboratory Assessments
Blood samples for ALT, AST, total bilirubin will be collected at Screening, Day 1, Weeks 4, 8, 
12, 16, 168, every 12 weeks thereafter, and the End of Study (EOS) Visit.
Blood samples for CMV will be collected at Screening and every 4 weeks thereafter throughout 
study participation.
Blood samples for ANC will be collected at Screening and every 2 weeks through Week 24.
Blood samples for Pneumococcal, Haemophilus Influenzae Type B (Hib), and Tetanus titers will 
be taken at screening


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Blood samples for immune-monitoring will be collected at Screening, Weeks 4, 12 and every 
12 weeks thereafter, and the EOS Visit: 
• 
Lymphocyte subset panel using flow cytometry (immunophenotyping) 
• 
Quantitative immunoglobulins: IgG, IgM, IgA 
• 
Serum CH50 level 
6.2.2.1. 
Evaluation for Gastrointestinal Events/Colitis 
For Grade 2 colitis and diarrhea (unless clinical diagnosis is established from medical history and 
physical examination), the following testing is required: 
• 
Stool culture for routine pathogens (Salmonella, Shigella, Campylobacter species, 
Clostridium diffi.cile toxin, Rotavirus, Cytomegalovirus, Adenovirus) 
• 
Stool for Ova and Parasites (Cryptosporidium parvum, Isospora belli, Enterocytozoon 
bieneusi, Septata intestinalis, Strongyloides, Microsporidia, Entamoeba histolytica, 
Cyclospora), Giardia antigen 
For grade 2' 3 or persistent grade 2 colitis or diarrhea without clear etiology (eg, clostridium 
diffi.cile enterocolitis), endoscopy with biopsy is required. All biopsy samples should include 
immunohistochemistry (IHC) and PCR for CMV, Adenovirus. 
PD 
6.2.2.2. 
Differentiation Between Small-bowel and Large-bowel Diarrhea 
Differentiation between small-bowel and large-bowel diarrhea: maybe possible on a clinical 
basis. If unclear, consider upper and lower tract endoscopy with biopsy. 
• 
Small bowel diarrhea is characterized by large volume diarrhea (more than one per day), 
possible associated dehydration weight loss and paraumbilical pain. Consider an endoscopic 
small-bowel biopsy and evaluate other etiologies such as celiac disease. 
• 
Large-bowel diarrhea may present with lower pelvic pain, tenesmus, generally smaller stool 
volume with gross blood frquently found in the stool. Consider a colonoscopic evaluation 
and biopsy. 
6.3. 
End of Study 
Subjects will be withdrawn from this study if they develop progressive disease, unacceptable 
toxicity related to idelalisib, withdraw consent, are noncompliant, or are lost to follow up or die. 
In this event, the following procedures should be performed: 
• 
Return ofused and unused drug supply 
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
Recording of all Grade AEs and all SAEs

Investigator Response Assessment

Laboratory assessments as outlined in Table 6-1

Recording of the reason for withdrawal

Deaths occurring within 30 days following the last dose of idelalisib, even if occurring after 
the End of Study Visit, will be captured.


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Table 6-1. 
Schedule of Study Procedures 
Period 
Screen 
Treatment 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15+ 
Week 
-4 
0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
Within 
Q4 
Q12 
End of 
Study Day 
-28 days 
1 
14 
28 
42 
52 
70 
84 
98 
112 
126 
140 
154 
168 
weeks 
weeks 
study 
Visit Window 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±7 
±7 
Infonned consent 
X 
Serum ~-HCG" 
X 
Pneumococcal, Hib, 
X 
Tetanus titers 
AL T I AST /total bilirubin 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test" 
X 
X 
X 
X 
X 
X 
X 
X 
ANCb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CMV surveillance 
X 
X 
X 
X 
X 
X 
X 
xc 
Immune Monitoring 
X 
X 
X 
X 
X 
X 
Assess adverse events and 
X 
X 
X 
X 
X 
X 
X 
X 
SAEsd 
Record concomitant 
X 
X 
X 
X 
X 
X 
X 
X 
medications< 
Idelalisib 
X 
X 
X 
X 
X 
X 
X 
X 
dispensing/accounting 
Investigator response 
assessmentr 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: 0-HCG=beta hmnan chorionic gonadotropin, AL T=alanine aminotransferase, AST=aspartate aminotransferase, Hib = Haemophilus Influenzae Type B 
a 
For women of child bearing potential; Serum 0 -HCG to be collected to be collected at screening, urine pregnancy test to be collected at visits from first dose of idelalisib to 
EOS 
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b
Absolute neutrophil count (ANC) will be monitored at least every two weeks for the first 24 weeks of idelalisib treatment
c
CMV surveillance must be conducted approximately every 4 weeks throughout the course of idelalisib treatment
d
For an AE of Diarrhea/Colitis: 1) Obtain history of onset and duration of diarrhea, including description of number of stools and stool composition, travel history, dietary 
changes and a medication review to identify possible diarrheogenic agents and 2) Perform physical examination including assessment for fever, dizziness, abdominal 
pain/cramping, and weakness
e
Concomitant medications only collected if it is related to an AE
f
Record investigator response assessment if obtained per standard of care


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Lymphocytosis

Laboratory abnormalities not requiring clinical intervention or further investigation. Such 
abnormalities will be captured as part of overall laboratory monitoring.

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
CRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death


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
Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to idelalisib interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Idelalisib and Procedures
The investigator or qualified sub-investigator is responsible for assessing the relationship to 
idelalisib therapy using clinical judgment and the following considerations:


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
No: Evidence exists that the adverse event has an etiology other than idelalisib. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg., venipuncture)
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the CTCAE, Version 4.03 and available at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or
Grade 5 (fatal) to describe the maximum intensity of the adverse event. For purposes of 
consistency with the CTCAE, these intensity grades are defined in Table 7-1.
Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Sign or symptom is present, but it is easily tolerated, is not expected to have a 
clinically significant effect on the subject’s overall health and well-being, does 
not interfere with the subject’s usual function, and is not likely to require 
medical attention.
Grade 2
Moderate
Sign or symptom causes interference with usual activity or affect clinical status, 
and may require medical intervention.
Grade 3
Severe
Sign or symptom is incapacitating or significantly affects clinical status and 
likely requires medical intervention and/or close follow-up.
Grade 4
Life-threatening
Sign or symptom results in a potential threat to life.
Grade 5
Fatal
Sign or symptom results in death.


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The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events listed in Section 7.1.2.
7.3.
Recommendations for Evaluation, Intervention, and Drug Discontinuation 
for Specific Adverse Events or Conditions
7.3.1.
Dermatological Events (Idelalisib)
Subjects receiving idelalisib with ≥Grade 3 rash have generally presented with a maculopapular 
rash on the trunk and extremities that is occasionally associated with fever and/or pruritus and 
responded to treatment with diphenhydramine and/or topical or oral corticosteroids. 
For subjects who develop a severe rash for which an underlying etiology cannot be identified 
(e.g., infection, co-suspect drug), study drug should be interrupted. Resumption of study drug 
should be considered once rash resolves.
Severe cutaneous reactions, including fatal events of Stevens-Johnson syndrome (SJS) and 
toxic epidermal necrolysis (TEN), have been reported in subjects receiving idelalisb. Assessment 
of potential causal association between idelalisib and the occurrence of SJS or TEN has been 
confounded by the coadministration of antineoplastic agents (e.g., bendamustine, rituximab) 
and/or other concomitant medications known to be associated with SJS or TEN (e.g., 
allopurinol). If SJS or TEN is suspected, idelalisib and all coadministered medications associated 
with SJS or TEN should be interrupted and the subject treated accordingly. 
Subjects should be monitored for the development of SJS, TEN, or other severe cutaneous 
reactions and idelalisib treatment should be discontinued if such events occur.
7.3.2.
Gastrointestinal Events
Isolated cases of gastrointestinal inflammation (eg, stomatitis, colitis, cecitis) have been noted in 
subjects receiving idelalisib. Rare cases of gastrointestinal perforation have occurred, generally 
in the setting of occult carcinoma, mesenteric embolus or diverticular disease.  Study treatment 
(idelalisib/placebo) should be discontinued in subjects who experience bowel perforation
Cholangitis manifest as hyperbilirubinemia out of proportion to serum transaminase elevations 
has been observed. While disease-related factors, neutropenia, toxicity from prior therapies, 
effects of ongoing supportive care, or pre-existing cholelithiasis may have initiated such events, 
it is possible that idelalisib played a contributory role. In such subjects, rechallenge with 
idelalisib has been possible and has not been associated with other severe adverse events. 
Subjects who have developed evidence of enteritis during idelalisib therapy have been 
successfully treated with antidiarrheals (eg, loperamide) and with enteric steroidal (eg, 
budesonide) or non-steroidal (eg sulfasalazine [Azulfidine®]) anti-inflammatory agents and have 
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For study subjects who develop severe abdominal pain the possibility of a bowel obstruction or 
perforation should be considered. Appropriate clinical and radiographic examination should be 
performed and supportive care or surgical intervention should be considered. Upon recovery, 
rituximab may be resumed.
For subjects who develop persistent diarrhea, causes related to concomitant medications or 
gastrointestinal infections such as Clostridium difficile (particularly for patients recently treated 
with broad spectrum antibiotics), Shigella, Campylobacter, Yersinia and CMV should be 
considered and treated if appropriate. Depending upon the clinical circumstances, endoscopy and 
biopsy, with bacterial and viral IHC staining should be considered. In the event that an infectious 
cause is not identified, an antimotility agent (eg, loperamide) may lessen symptoms and 
intervention with enteric steroidal (eg, budesonide) or non-steroidal (eg, sulfasalazine) 
anti-inflammatory agents should be considered. In such subjects, rechallenge with idelalisib at a 
lower dose level has resulted in recurrence of symptoms in some but not all subjects and has not 
been associated with other severe adverse events.
7.3.2.1.
Investigation for Idelalisib Late Onset or Severe Diarrhea/Colitis
See CTCAE Version 4.03 for definitions of colitis and diarrhea.
Among idelalisib-treated patients who reported diarrhea or colitis, the median time to onset of 
any grade diarrhea or colitis was 1.9 months (range, 0.0–29.8), of grade 1 or 2 was 1.5 months 
(range, 0.0–15.2) and of grade 3 or 4 was 7.1 months (range, 0.5–29.8). Kaplan–Meier curves of 
time to onset of diarrhea or colitis are shown for all idelalisib- treated patients in Figure 7-1
{Coutre et al 2015}.
Figure 7-1.
Kaplan-Meier Time to Diarrhea or Colitis


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Idelalisib-associated severe diarrhea responds poorly to antimotility agents however, median 
time to resolution ranged between 1 week and 1 month across trials following interruption of 
idelalisib treatment and, in some instances, initiation of corticosteroid treatment {Gilead 
Sciences Inc 2014}.
7.3.3.
Hepatic Events
Transaminase Elevations: Consistent with observations in a dog toxicology study, reversible 
asymptomatic ALT/AST increases were also observed early in the idelalisib program in phase 1 
studies (101-02 and 101-07) in subjects with hematologic malignancies. Transaminase elevations 
generally occurred within 4 to 12 weeks of drug initiation, and resolved spontaneously over a 
period of 2 to 4 weeks with drug being continued for Grade 1 and 2 elevations and drug withheld 
for Grade 3 or 4 elevations until resolution. These early observations have been consistent with 
the ongoing experience with idelalisib treatment and transaminase elevations are now well 
characterized as most frequently asymptomatic, transient and occurring within the first 3 months 
of treatment.
Grade 1 or 2 elevations commonly resolve despite continued idelalisib treatment and Grade 3 or 
4 elevations can be managed by temporarily withholding idelalisib. Successful rechallenge after 
resolution at either the same or lower dose level of idelalisib has been achieved in the majority of 
subjects. There has been no evidence of impaired synthetic function. Close monitoring of hepatic 
laboratory tests during therapy is important to allow for appropriate idelalisib interruption and 
reinstitution so that subjects may continue with study drug treatment.
7.3.4.
Hematological and Immunological Events
In the Phase 1 experience with idelalisib in patients with NHL and CLL, subjects with Grade 3 
neutropenia, anemia, and/or thrombocytopenia were enrolled to clinical trials. Decreased levels 
of neutrophil counts, hemoglobin, or platelet counts during idelalisib administration were largely 
due to minor fluctuations in these parameters among subjects with pre-existing hematological 
abnormalities due to disease or prior therapy. Thus, idelalisib did not appear to induce overt 
myelosuppression. Obvious patterns of drug-mediated reductions in circulating CD4+ 
lymphocyte counts or suppression of serum IgG levels were also not observed.
Treatment-emergent Grade 3 or 4 neutropenia events, including febrile neutropenia, have 
occurred in subjects treated with idelalisib. All subjects should have their blood counts 
monitored at least every 2 weeks for the first 6 months of idelalisib treatment. For subjects who 
develop ANC 0.5 to < 1.0 Gi/L, blood counts should be monitored at least weekly. For subjects 
who develop ANC < 0.5 Gi/L, idelalisib should be interrupted and blood counts monitored at 
least weekly until ANC is ≥0.5 Gi/L, at which point, idelalisib dosing may be resumed at 
100 mg BID.  Neutropenia should be managed according to established clinical guidelines.
No modification of any drug for changes in circulating CD4+ counts or Ig levels is planned.


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7.3.5.
Pulmonary Events
Documented bacterial, fungal, viral, and pneumocystis pneumonias have been observed in 
patients receiving idelalisib, primarily in patients with CLL. Some study subjects receiving 
idelalisib alone or in combination have developed evidence of pneumonitis without documented 
pulmonary infection. 
Given the potential for infectious or drug-related pulmonary adverse events, clinicians should be 
particularly observant for evidence of respiratory events in subjects participating in this trial. 
Subjects who describe pulmonary symptoms (eg, dyspnea on exertion, cough, 
shortness of breath); manifest a decline from baseline of 5% in oxygen saturation, or 
demonstrate evidence of pulmonary inflammation (eg, focal or diffuse interstitial pattern or 
ground-glass opacities on chest CT) should be evaluated. Potential bacterial, fungal, or viral 
etiologies should be assessed. Noninfectious etiologies such as pulmonary edema or 
thromboembolism should also be considered.
As appropriate for the clinical situation and culture results, subjects should be treated empirically 
or given specific antibiotics, antifungals, or antiviral agents for a cultured organism. Supportive 
care, including oxygen or mechanical ventilation, should be provided as necessary.
For subjects with suspected pneumonitis (eg, onset of cough, dyspenea, hypoxia and/or a diffuse 
interstitial pattern or ground-glass opacities on chest imaging without obvious infectious 
etiology), idelalisib/placebo should be discontinued and therapy with systemic corticosteroids
(eg, prednisone, 60mg/day) should be instituted rapidly {Liote et al 2010}. Supportive care, 
including oxygen or mechanical ventilation, should be provided as necessary.
7.3.6.
Secondary Malignancies
Subjects receiving idelalisib for CLL or iNHL have developed pre-malignant and secondary 
malignant diseases, such as basal cell carcinoma, myelodysplastic syndrome, myeloproliferative 
disorders, and more aggressive lymphoid malignancies (eg, have had Richter transformation). 
Generally this has occurred in subjects who have received multiple previous lines of therapy and 
when idelalisib is combined with other therapies such as rituximab or bendamustine. The specific 
association of the therapeutic agents with these types of events has not been determined.
There are reports of pre-malignant and malignant diseases that have developed in subjects who 
have been treated with bendamustine, including myelodysplastic syndrome, myeloproliferative 
disorders, acute myeloid leukemia, and bronchial carcinoma. The specific association of the 
therapeutic agents with these types of events has not been determined.
7.3.7.
Tumor Lysis Syndrome
Tumor lysis syndrome has not been observed with idelalisib monotherapy. 
When idelalisib is combined with other agents known to induce tumor lysis syndrome, 
prophylaxis with agents such as allopurinol may be considered. The benefit versus risk of 


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prophylactic agents must be carefully considered given a potential of increased risk of severe 
skin toxicity.
Subjects with tumor lysis syndrome should receive rapid reversal of hyperkalemia, intravenous 
hydration, antihyperuricemic agents, and appropriate cardiac and renal support, including 
dialysis as indicated. Upon recovery to baseline functioning, such subjects should continue study 
treatment including study drug (idelalisib/placebo).
7.4.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
All SAEs, regardless of cause or relationship, that occur after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) or designee as instructed. 
This also includes any SAEs resulting from protocol-associated procedures performed from 
screening onwards.
All AEs, regardless of cause or relationship, that occur from initiation of study medication until 
30 days after last administration of idelalisib must be reported to the eCRF database as 
instructed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of idelalisib, regardless of causality, should also be reported.
All AEs should be followed up until resolution if possible. If by the last day on study (including 
the off-study medication follow-up period) the AE has not resolved, then the AE will be 
followed up until the investigator and/or Gilead Sciences determine that the subject's condition is 
stable. However, Gilead Sciences may request that certain AEs be followed until resolution.
Investigators are not obligated to actively seek SAEs after the 30 day period. However, if the 
investigator learns of any SAEs that occur after study participation has concluded and the event 
is deemed relevant to the use of idelalisib, he/she should promptly document and report the event 
to Gilead DSPH or designee as instructed.
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guidelines.
7.4.1.
Serious Adverse Event (eSAE) Reporting Process 
Site personnel record the SAE on the paper serious adverse event reporting form and submit via 
fax to Gilead DSPH within 24 hours.
All AEs and SAEs will be recorded in the CRF/eCRF database within the timelines outlined in 
the CRF/eCRF completion guideline.
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 


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Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
Additional information may be requested to ensure the timely completion of accurate safety 
reports.
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/eCRF and the event description section of the SAE 
form.
7.5.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with idelalisib. The investigator should notify the IEC of SUSAR reports as soon as is practical, 
where this is required by local regulatory agencies, and in accordance with the local institutional 
policy. 
7.5.1.
Reporting of Adverse Events Relating and Other Anticipated Medical Events 
in the Study Population
Given the endpoints of the study and in order to maintain the integrity of the study, the following 
events that are assessed as unrelated to idelalisib will not be considered SAEs:

Progression of lymphoid malignancy

Death related to progression of lymphoid malignancy

Disease progression and death from disease progression should be reported as SAEs by the 
investigator only if it is assessed that the idelalisib caused or contributed to the disease 
progression (ie, by a means other than lack of effect).  Unrelated disease progression should 
be captured on the eCRF.
These will be reported, as appropriate, in the final clinical study report and in any relevant 
aggregate safety reports.


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7.5.2.
Toxicity Management 
See Table 5-2 for more information related to recommended dose modifications associated with 
toxicities. Please refer to the current idelalisib IB for information related to toxicity management.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study to the Gilead DSPH using the pregnancy 
report form within 24 hours of becoming aware of the pregnancy.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.


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A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post 
study must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH  using the pregnancy outcome 
report form. If the end of the pregnancy occurs after the study has been completed, the outcome 
should be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: 
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477. 
Pregnancies of female partners of male study subjects exposed to idelalisib must also be reported 
and relevant information should be submitted to Gilead DSPH using the pregnancy and 
pregnancy outcome forms within 24 hours. Monitoring of the subject should continue until the 
conclusion of the pregnancy. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead DSPH, fax number +1 650 522-
5477 or email Safety_FC@gilead.com. 
Refer to Appendix 2 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports (excluding pregnancy) must be reported on the special 
situations report form and forwarded to Gilead DSPH within 24 hours of the investigator 
becoming aware of the situation. These reports must consist of situations that involve idelalisib, 
but do not apply to concomitant medications. Except for situations that result in AEs, special 
situations involving concomitant medication will not be reported. Any inappropriate use of 
concomitant medications prohibited by this protocol should not be reported as “misuse,” but may 
be more appropriately documented as a protocol deviation.
Refer to the CRF/eCRF completion guidelines for full instructions on the mechanism of special 
situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE CRF/eCRF and/or the SAE report form. Details of the symptoms 
and signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives
As noted in Section 2, the primary objective is to provide idelalisib to subjects receiving
GS-9820 in Study GS-US-315-0102 at the time of study closure who have had objective 
evidence of clinical benefit defined as at least stable disease on imaging assessed by the IRC and 
no toxicities prior to enrollment in this study that would preclude initiating therapy with 
idelalisib.
8.2.
Safety Endpoints
Safety will be assessed with endpoints including incidence of ≥Grade 3 AEs, SAEs, and deaths.
8.3.
Analysis Sets
Both safety and efficacy will be assessed using data collected from subjects who received at least 
1 dose of idelalisib.
8.4.
Analysis Methods
All the analyses will be limited to descriptive summaries and listings. Categorical variables will 
be summarized with the number and percentage of subjects in each category. Continuous 
variables will be summarized by presenting n, mean, standard deviation, median, Q1, Q3, 
minimum and maximum.
8.5.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable sub-investigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any sub-investigator’s) participation in the study. The investigator and 
sub-investigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Independent Ethics Committee (IEC) Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IEC. The investigator will not begin any study subject activities until 
approval from the IEC has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IEC any modifications made to the protocol or any accompanying material to be provided to 
the subject after initial IEC approval, with the exception of those necessary to reduce immediate 
risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IEC-approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately signed 


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and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IEC or local 
requirements. 
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form submitted to the Sponsor. NOTE: The investigator must keep a screening log showing 
codes, names, and addresses for all subjects screened and for all subjects enrolled in the trial.
Subject data will be processed in accordance with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, CRF/eCRF, idelalisib, and any other study information, 
remain the sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IEC
and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);
— Birth dates will be collected as per local regulatory requirements, as needed

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);


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
Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of idelalisib, including dates of dispensing and 
return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 
data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), the investigator will use his/her log in 


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credentials to confirm that the forms have been reviewed, and that the entries accurately reflect 
the information in the source documents. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (eg data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Drug Accountability and Return
Gilead recommends that used and unused idelalisib supplies be returned to the shipping facility 
from which it came for eventual destruction. The study monitor will provide instructions for 
return. If return is not possible, the study monitor will evaluate each study center’s disposal 
procedures and provide appropriate instruction for destruction of unused idelalisib supplies. If 
the site has an appropriate standard operating procedure (SOP) for drug destruction as 
determined by Gilead QA, the site may destroy used (empty or partially empty) and unused 
idelalisib supplies in accordance with that site’s approved SOP. A copy of the site’s approved 
SOP will be obtained for central files. 
If idelalisib is destroyed on site, the investigator must maintain accurate records for all idelalisib
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the idelalisib. Upon study completion, copies of 
the idelalisib accountability records must be filed at the site. Another copy will be returned to 
Gilead.
The study monitor will review idelalisib supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to appropriately qualified personnel from Gilead Sciences or 
its representatives, to IECs, or to regulatory authority or health authority inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IEC in 


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accordance with local requirements and receive documented IEC approval before modifications 
can be implemented.
9.2.2.
Communications with Regulatory Authorities
Gilead Sciences, working either directly or through designees, will assume responsibility for 
regulatory interactions with relevant regulatory authorities. Gilead Sciences will maintain an 
IND for idelalisib in support of the study in the United States and will maintain similar 
regulatory applications with other regulatory authorities, as required for conduct of the study. In 
fulfilling this responsibility, Gilead Sciences (or a designee) will collect, assemble, and 
communicate all required regulatory documents (eg, Form FDA 1572, investigator financial 
disclosure forms, protocol and protocol amendments, investigator brochures, informed consent 
documents, annual reports) as required by regulation. Gilead Sciences (or a designee) will also 
assume responsibility for adverse event reporting to regulatory authorities as described in 
Section 7.5.
9.2.3.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). Gilead 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly 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.
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg attendance at Investigator's Meetings.  If required under the applicable statutory and 


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regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
CRF/eCRF.
The monitor is responsible for routine review of the CRF/eCRF at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the CRF/eCRF. The investigator agrees to cooperate with the monitor to 
ensure that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies) and IECs. In terminating the study, Gilead and the investigator will 
assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
Coutre S, Byrd J, Furman R, Brown J, et al. Phase I study of CAL-101, an isoform-selective 
inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously 
treated chronic lymphocytic leukemia [Abstract]. 47th Annual Meeting of the 
American Society of Clinical Oncology (ASCO); 2011 June 3; Chicago, IL. 
Coutre SE, Barrientos JC, Brown JR, de Vos S, Furman RR, Keating MJ, et al. Management of 
adverse events associated with idelalisib treatment - expert panel opinion. Leuk 
Lymphoma 2015:1-20.
Di Bella N, Taetle R, Kolibaba K, Boyd T, Raju R, Barrera D, et al. Results of a phase 2 study of 
bortezomib in patients with relapsed or refractory indolent lymphoma. Blood 
2010;115 (3):475-80.
Diehl V, Thomas RK, Re D. Part II: Hodgkin's lymphoma--diagnosis and treatment. Lancet 
Oncol 2004;5 (1):19-26.
Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia. Lancet 2008;371 (9617):1017-29.
Eichhorst B, Hallek M, Dreyling M. Chronic lymphocytic leukaemia: ESMO Clinical Practice 
Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21 Suppl 
5:v162-4.
Friedberg JW. New strategies in diffuse large B-cell lymphoma: translating findings from gene 
expression analyses into clinical practice. Clin Cancer Res 2011;17 (19):6112-7.
Gilead Sciences Inc. ZYDELIG® (idelalisib) tablets, for oral use. U.S. Prescribing Information. 
Foster City, CA. July 2014:
Gilead Sciences Limited. Zedelig (idelalisib) 150mg. Summary of Product Characteristics. 
Cambridge,United Kingdom. Revised  21 July.  2015:
Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Bortezomib in 
patients with relapsed or refractory mantle cell lymphoma: updated time-to-event 
analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 2009;20 
(3):520-5.
Gribben JG, O'Brien S. Update on therapy of chronic lymphocytic leukemia. J Clin Oncol 
2011;29 (5):544-50.
Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of 
rituximab to fludarabine and cyclophosphamide in patients with chronic 
lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376 
(9747):1164-74.


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Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, et al. Phase III study 
to evaluate temsirolimus compared with investigator's choice therapy for the 
treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27 
(23):3822-9.
Hoppe RT, Advani RH, Ambinder RF, Bierman PJ, Bloomfield CD, Blum K, et al. Hodgkin 
disease/lymphoma. J Natl Compr Canc Netw 2008;6 (6):594-622.
Jost L. Hodgkin's disease: ESMO clinical recommendations for diagnosis, treatment and follow-
up. Ann Oncol 2007;18 (Suppl 2):ii53-4.
Kahl B, Byrd J, Flinn I, Wagner-Johnston N, Spurgeon S, al E. Significant Clinical Activity Of 
Cal-101, An Isoform-Selective Inhibitor Of Phosphatidylinositol 3 Kinase P110D, 
In Patients With Relapsed Or Refractory Indolent And Mantle Cell Lymphoma 
[Abstract 350] 11th Triennial International Conference on malignant Lymphoma 
(Icml). Lugano, Swizterland: 2011:
Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, et al. Therapeutic role of alemtuzumab 
(Campath-1H) in patients who have failed fludarabine: results of a large 
international study. Blood 2002;99 (10):3554-61.
Kuruvilla J. Standard therapy of advanced Hodgkin lymphoma. Hematology / the Education 
Program of the American Society of Hematology. American Society of 
Hematology 2009:497-506.
Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B, et al. Immunochemotherapy 
with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone 
significantly improves response and time to treatment failure, but not long-term 
outcome in patients with previously untreated mantle cell lymphoma: results of a 
prospective randomized trial of the German Low Grade Lymphoma Study Group 
(GLSG). J Clin Oncol 2005;23 (9):1984-92.
Liote H, Liote F, Seroussi B, Mayaud C, Cadranel J. Rituximab-induced lung disease: A 
systematic literature review. Eur Respir J 2010;35 (3):681-7.
Moskowitz AJ, Perales MA, Kewalramani T, Yahalom J, Castro-Malaspina H, Zhang Z, et al. 
Outcomes for patients who fail high dose chemoradiotherapy and autologous stem 
cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J 
Haematol 2009;146 (2):158-63.
Okkenhaug K, Vanhaesebroeck B. PI3K-signalling in B- and T-cells: insights from gene-
targeted mice. Biochemical Society transactions 2003;31 (Pt 1):270-4.
Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin 
prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic 
review and meta-analysis. Leuk Lymphoma 2009;50 (5):764-72.


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Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, et al. Intensified 
chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab 
for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label 
randomised phase 3 trial. Lancet 2011;378 (9806):1858-67.
Salles GA. Clinical features, prognosis and treatment of follicular lymphoma. Hematology / the 
Education Program of the American Society of Hematology. American Society of 
Hematology 2007:216-25.
Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, et al. Long-term results of 
combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority 
of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol 1987;5 
(1):27-37.
Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T, et al. Immunochemotherapy with 
rituximab and overall survival in patients with indolent or mantle cell lymphoma: 
a systematic review and meta-analysis. J Natl Cancer Inst 2007;99 (9):706-14.
Surveillance Epidemiology and End Results (SEER) Program. SEER Stat Fact Sheets: Chronic 
Lymphocytic Leukemia. Available at: 
http://seer.cancer.gov/statfacts/html/clyl.html. Accessed 12 May 2011.
Vanhaesebroeck B, Ali K, Bilancio A, Geering B, Foukas LC. Signalling by PI3K isoforms: 
insights from gene-targeted mice. Trends Biochem Sci 2005;30 (4):194-204.
Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, et al. Ofatumumab 
as single-agent CD20 immunotherapy in fludarabine-refractory chronic 
lymphocytic leukemia. J Clin Oncol 2010;28 (10):1749-55.
Williams ME, Dreyling M, Winter J, Muneer S, Leonard JP. Management of mantle cell 
lymphoma: key challenges and next steps. Clinical lymphoma, myeloma & 
leukemia 2010;10 (5):336-46.
Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Bellam N, et al. Non-
Hodgkin's lymphomas. J Natl Compr Canc Netw 2011;9 (5):484-560.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


ldelalisib 
Protocol GS-US-313-2120 
Gilead Sciences, Inc. 
Appendix 1. 
Investigator Signarore Page 
GILEAD SCIENCES, INC. 
199 EAST BLAINE STREET 
SEATTLE, WA 98102 
STUDY ACKNOWLEDGEMENT 
Final 
Amendm.ent 1 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects Previously Treated with the 
Investigational PI3Ko lnhibitor, GS-9820 
Amendment 1 28 March 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PD 
Mario Marcondes, MD 
Gilead Medical Monitor 
~STIGATORSTATEMENT 
1 have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
l will provide all study personnel under my supervision copies of the protocol and access to aU 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 55 
28 March 2016 


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Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a) Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause.  In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b) Definition of Male Fertility
For the purposes of this study, a male born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Idelalisib has insufficient data to exclude the possibility of a clinically relevant interaction with 
hormonal contraception that results in reduced contraception efficacy.  Therefore, contraceptive 
steroids are not recommended as a contraceptive method either solely or as a part of a 
contraceptive regimen.  Data from clinical pharmacokinetic interaction studies of idelalisib have 
demonstrated no adverse effect on fertility or embryo-fetal development.  However, there is no 
clinical data of idelalisib in pregnant women.  Please refer to the latest version of the 
investigator’s brochure for additional information. 
b) Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires using a highly effective 
contraceptive measure.  They must also not rely on hormone-containing contraceptives as a form 
of birth control during the study.  They must have a negative serum pregnancy test at Screening 
and a negative pregnancy test on the Baseline/Day 1 visit prior to randomization.  At minimum, a 
pregnancy test will be performed at the end of relevant systemic exposure.  In the event of a 
delayed menstrual period (over one month between menstruations), a pregnancy test must be 
performed to rule out pregnancy.  This is even true for women of childbearing potential with 
infrequent or irregular periods.  They must also agree to one of the following from Screening 
until 30 days after the end of relevant systemic exposure.


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Complete abstinence from intercourse of reproductive potential.  Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual lifestyle.
Or
Consistent and correct use of 1 of the following methods of birth control listed below. 

Intrauterine device (IUD) with a failure rate of <1% per year

Tubal sterilization

Ensure micro-insert system (provided confirmation of success 3 months after procedure)

Vasectomy in the male partner (provided that the partner is the sole sexual partner and had 
confirmation of surgical success 3 months after procedure)

Barrier methods (one female barrier and one male barrier must be used in combination)
— Female barriers: Diaphragm with spermicide or Cervical cap with spermicide
— Male barriers: Male condom (with or without spermicide)
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 30 days after the end of relevant systemic exposure
3) Contraception Requirements for Male Subjects
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment until the end of relevant 
systemic exposure.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM).  Female condom and male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last idelalisib dose. Subjects who become 
pregnant or who suspect that they are pregnant during the study must report the information to 


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the investigator and discontinue idelalisib immediately. Subjects whose partner has become 
pregnant or suspects she is pregnant during the study must report the information to the 
investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome 
are outlined in Section 7.6.2.1.

Prot_000.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Director 
or Clinical Program 
Manager: 
Gilead Medical 
Monitor: 
(!') GILEAU 
CLINICAL STUDY PROTOCOL 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Ko Inhibitor, GS-9820 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
NIA 
2015-005766-39 
Lymphoid Malignancies 
GS-US-313-2120 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
pp 
PPD 
t-'t-'U 
Lyndah Dreiling 
pp 
PPD 
Protocol Version/Date: 
Original: 05 Januaty 2016 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The infonnation is only to be used by you in 
com1ection with authorized clinical studies of the investigational dmg described in the protocol. 
You will not disclose any of the infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessaty to obtain infotmed consent from those 
persons to whom the dmg may be administered. 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
PROTOCOL SYNOPSIS ..............................................................................................................................................5
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS......................................................................8
1.
INTRODUCTION ................................................................................................................................................9
1.1.
Background ..............................................................................................................................................9
1.2.
Idelalisib...................................................................................................................................................9
1.3.
Rationale for This Study ........................................................................................................................10
1.4.
Benefit/Risk Assessment for the Study..................................................................................................10
1.5.
Compliance ............................................................................................................................................10
2.
OBJECTIVES.....................................................................................................................................................11
3.
STUDY DESIGN................................................................................................................................................12
3.1.
Endpoints ...............................................................................................................................................12
3.2.
Study Design..........................................................................................................................................12
3.3.
Study Treatments ...................................................................................................................................12
3.4.
Duration of Treatment............................................................................................................................12
3.5.
Discontinuation Criteria.........................................................................................................................12
3.6.
Source Data............................................................................................................................................13
3.7.
Biomarker Testing..................................................................................................................................13
4.
SUBJECT POPULATION..................................................................................................................................14
4.1.
Number of Subjects and Subject Selection ............................................................................................14
4.2.
Inclusion Criteria....................................................................................................................................14
4.3.
Exclusion Criteria...................................................................................................................................14
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................16
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................16
5.2.
Description and Handling of Study Treatments .....................................................................................16
5.2.1.
Formulation..........................................................................................................................16
5.2.2.
Packaging and Labeling .......................................................................................................16
5.2.3.
Storage and Handling...........................................................................................................16
5.2.4.
Dosage and Administration of Idelalisib..............................................................................17
5.2.5.
Dispensing............................................................................................................................17
5.2.6.
Premedication.......................................................................................................................17
5.2.7.
Administration Instructions..................................................................................................17
5.2.8.
Dosing Schedule...................................................................................................................17
5.2.9.
Dose Levels..........................................................................................................................18
5.2.10.
Idelalisib Dose Adjustments.................................................................................................18
5.3.
Prior and Concomitant Medications.......................................................................................................19
5.3.1.
Anticancer or Experimental Therapies Other than Investigational 
Treatments............................................................................................................................20
5.3.2.
Antibiotics............................................................................................................................20
5.3.3.
Antidiarrheals.......................................................................................................................20
5.3.4.
Corticosteroids .....................................................................................................................20
5.3.5.
Granulocyte Colony-Stimulating Factors and Erythropoietin..............................................20
5.3.6.
Drugs that Alter CYP3A-Dependent Metabolism................................................................20
5.3.7.
Drugs that undergo CYP3A-Dependent Metabolism...........................................................21
5.3.8.
Immunization .......................................................................................................................21


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5.3.9.
Ultraviolet Exposure ............................................................................................................21
5.3.10.
Surgery .................................................................................................................................22
5.4.
Accountability for Idelalisib...................................................................................................................22
5.4.1.
Overdose Precautions...........................................................................................................22
5.4.2.
Inadvertent Exposure and Spill Precautions.........................................................................22
5.4.3.
Investigational Medicinal Product Return or Disposal.........................................................23
5.5.
Discontinuation from Study ...................................................................................................................23
6.
STUDY PROCEDURES ....................................................................................................................................24
6.1.
Subject Enrollment.................................................................................................................................24
6.1.1.
Subject Recruitment .............................................................................................................24
6.1.2.
Subject Compensation for Participation...............................................................................24
6.1.3.
Screening Visit .....................................................................................................................24
6.2.
Treatment Assessments..........................................................................................................................24
6.2.1.
Clinical Evaluation...............................................................................................................25
6.3.
End of Study...........................................................................................................................................25
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................27
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................27
7.1.1.
Adverse Events.....................................................................................................................27
7.1.2.
Serious Adverse Events........................................................................................................27
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................28
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................28
7.2.1.
Assessment of Causality for Idelalisib and Procedures........................................................28
7.2.2.
Assessment of Severity ........................................................................................................29
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................29
7.3.1.
Serious Adverse Event (eSAE) Reporting Process ..............................................................30
7.4.
Gilead Reporting Requirements.............................................................................................................30
7.4.1.
Reporting of Adverse Events Relating and Other Anticipated Medical 
Events in the Study Population ............................................................................................31
7.4.2.
Toxicity Management...........................................................................................................31
7.5.
Special Situations Reports......................................................................................................................31
7.5.1.
Definitions of Special Situations..........................................................................................31
7.5.2.
Instructions for Reporting Special Situations.......................................................................32
8.
STATISTICAL CONSIDERATIONS................................................................................................................34
8.1.
Analysis Objectives................................................................................................................................34
8.2.
Safety Endpoints ....................................................................................................................................34
8.3.
Analysis Sets..........................................................................................................................................34
8.4.
Analysis Methods...................................................................................................................................34
8.5.
Adverse Events.......................................................................................................................................34
9.
RESPONSIBILITIES..........................................................................................................................................35
9.1.
Investigator Responsibilities ..................................................................................................................35
9.1.1.
Good Clinical Practice..........................................................................................................35
9.1.2.
Independent Ethics Committee (IEC) Review and Approval...............................................35
9.1.3.
Informed Consent.................................................................................................................35
9.1.4.
Confidentiality......................................................................................................................36
9.1.5.
Study Files and Retention of Records ..................................................................................36
9.1.6.
Case Report Forms...............................................................................................................37
9.1.7.
Drug Accountability and Return ..........................................................................................38
9.1.8.
Inspections............................................................................................................................38


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9.1.9.
Protocol Compliance............................................................................................................38
9.2.
Sponsor Responsibilities ........................................................................................................................38
9.2.1.
Protocol Modifications.........................................................................................................38
9.2.2.
Communications with Regulatory Authorities.....................................................................39
9.2.3.
Study Report and Publications .............................................................................................39
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................39
9.3.1.
Payment Reporting...............................................................................................................39
9.3.2.
Access to Information for Monitoring..................................................................................40
9.3.3.
Access to Information for Auditing or Inspections ..............................................................40
9.3.4.
Study Discontinuation..........................................................................................................40
10.
REFERENCES ...................................................................................................................................................41
11.
APPENDICES ....................................................................................................................................................44
Appendix 1.
Investigator Signature Page....................................................................................................45
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................46
LIST OF IN-TEXT TABLES
Table 5-1.
Idelalisib Dose Levels ............................................................................................................18
Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}.....................................................19
Table 6-1.
Schedule of Study Procedures................................................................................................26
Table 7-1.
Grading of Adverse Event Severity........................................................................................29


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
199 East Blaine Street
Seattle, WA 98102
Study Title: 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects 
Previously Treated with the Investigational PI3Kδ Inhibitor, GS-9820
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
Not Applicable
2015-005766-39
Study Centers 
Planned:
2 centers in the Netherlands
Objectives:
The primary objective of this study is as follows:

To provide open-label idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure who have had
objective evidence of clinical benefit defined as at least stable 
disease on imaging assessed by an independent review committee 
(IRC) and no toxicities prior to enrollment in this study that 
would preclude initiating therapy with idelalisib. Idelalisib and 
GS-9820 are both in the class of agents that inhibit PI3Kδ and as 
such this exchange of class for class agent is warranted and 
acceptable.
Study Design:
This study is an open-label, rollover study to provide idelalisib to 
subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure.
Number of Subjects 
Planned:
Approximately 6 subjects
Target Population:
Subjects receiving GS-9820 in Study GS-US-315-0102 at the time of 
study closure who have objective evidence of clinical benefit defined 
as at least stable disease on imaging assessed by the IRC at final 
response assessment prior to enrollment in this study.
Duration of 
Treatment:
Subjects will be treated until progressive disease or intolerable 
toxicity.


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Diagnosis and Main 
Eligibility Criteria:
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be 
eligible for participation in this study:
1) Receiving GS-9820 in Study GS-US-315-0102 with objective 
evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC at the time of Study 
GS-US-315-0102 closure
2) For female subjects of childbearing potential, willingness to use a 
protocol recommended method of contraception during 
heterosexual intercourse from the signing of informed consent 
throughout the study treatment period and up to 30 days from the 
last dose of idelalisib (see Appendix 2)
3) For male subjects of reproductive potential having intercourse 
with females of childbearing potential, willing to use a protocol 
recommended method of contraception during heterosexual 
intercourse and to refrain from sperm donation throughout the 
study treatment period and for 90 days following discontinuation 
of idelalisib (see Appendix 2)
4) Willingness to comply with scheduled visits, drug administration 
plan, imaging studies, laboratory tests, other study procedures, 
and study restrictions. Note: Psychological, social, familial, or 
geographical factors that might preclude adequate study 
participation should be considered.
5) Evidence of a personally signed informed consent indicating that 
the subject is aware of the neoplastic nature of their disease and 
has been informed of the procedures to be followed, the 
experimental nature of the therapy, alternatives, potential benefits, 
possible side effects, potential risks and discomforts, and other 
pertinent aspects of study participation.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not
eligible to be enrolled in this study:
1) Known hypersensitivity or intolerance to any of the active 
substances or excipients in the formulation of idelalisib.
2) Toxicities that would preclude initiating therapy with idelalisib 
prior to enrollment (eg, history of drug-induced pneumonitis, 
ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding


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Study Procedures/
Frequency:
All subjects will receive idelalisib 150 mg taken orally, twice per day 
(BID) continuously. Subjects will undergo disease assessments and 
receive medical care per institutional standards of care.
Test Product, Dose, 
and Mode of 
Administration:
Idelalisib: 150 mg taken orally BID starting on Day 1 and 
administered continuously thereafter.
Reference Therapy, 
Dose, and Mode of 
Administration:
None
Criteria for 
Evaluation:
Safety:
Overall safety profile characterized by the type, frequency, severity, 
timing of onset, duration, and relationship to study therapy of ≥Grade 
3 adverse events (AEs), serious adverse events (SAEs), and deaths.
Efficacy:
Investigator response assessments
Statistical Methods:
Safety will be assessed by incidence of ≥ Grade 3 AEs, SAEs, and 
deaths. Efficacy will be evaluated by investigator response 
assessments. Both safety and efficacy will be assessed using data 
collected from subjects who received at least 1 dose of idelalisib. All 
analyses will be limited to descriptive summaries and listings.
Sample Size:
Up to 6 subjects
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
-HCG
beta human chorionic gonadotropin
BID
bis in die (twice daily)
CFR
Code of Federal Regulations
CLL
chronic lymphocytic leukemia
CRO
contract research organization
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DSPH
Drug Safety and Public Health
eCRF
electronic case report form
EOS
end of study
EU
European Union
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
G-CSF
granulocyte colony-stimulating factor
GCP
good clinical practice
GM-CSF
granulocyte-macrophage colony-stimulating factors
HLT
High-Level Term
HMG-CoA
3-hydroxy-3-methyl-glutaryl-Coenzyme A
IB
investigator’s brochure
ICH
International Conference on Harmonisation
iNHL
indolent non-Hodgkin lymphoma
IEC
independent ethics committee
IUD
intrauterine device
MCL
mantle cell lymphoma
NHL
non-Hodgkin lymphoma
PI3K
phosphatidylinositol 3-kinase
PDE5
phosphodiesterase-5
SAE
serious adverse event
SOC
system organ class
SOP
standard operating procedure
SADR
serious adverse drug reaction
SUSAR
suspected unexpected serious adverse reactions
ULN
upper limit of normal


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1.
INTRODUCTION
1.1.
Background
B-cell lymphoid malignancies comprise the most common hematological malignancies 
{Surveillance Epidemiology and End Results (SEER) Program 2011}. These cancers arise from 
the accumulation of monoclonal B lymphocytes in lymph nodes and often in organs such as 
blood, bone marrow, lymph nodes, spleen, and liver. Among the variants of these cancers are 
non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), indolent 
non Hodgkin lymphoma (iNHL), and mantle cell lymphoma (MCL), as well as chronic 
lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL). These disorders are characterized 
by lymphadenopathy that is frequently disturbing for patients and can sometimes induce life 
threatening organ dysfunction; patients may also have constitutional symptoms (fevers, night 
sweats, and/or weight loss) and fatigue {Diehl et al 2004}, {Salles 2007}, {Dighiero et al 2008}, 
{Williams et al 2010}. 
The goal of therapy for these diseases is to induce tumor regression and delay tumor progression 
in order to control disease-related complications and potentially extend life. Patients who require 
treatment are commonly given chemotherapeutic and/or immunotherapeutic agents {Hoppe et al 
2008}, {Jost 2007} {Eichhorst et al 2010}, {Friedberg 2011}, {Gribben et al 2011}, {Zelenetz et 
al 2011}. Among patients with iNHL, CLL, and MCL, front line combination therapies can be 
effective in providing durable remissions {Lenz et al 2005}, {Santoro et al 1987}, {Schulz et al 
2007}, {Hallek et al 2010}, {Recher et al 2011}. In DLBCL and HL, such front-line regimens 
can be curative in the majority of patients {Santoro et al 1987}, {Kuruvilla 2009}, {Recher et al 
2011}. However, most treated patients with iNHL, CLL, and MCL will eventually experience 
disease relapse. Some patients with DLBCL or HL will experience recurrent disease even with 
initial induction therapy and later salvage therapy. For any of these cancers, further sequential 
therapies are given in an attempt to control disease manifestations. Despite use of agents with 
differing mechanisms of action, progressive resistance to treatment develops. Patients with 
progressive disease have a poor prognosis; median survival for these groups of patients is 
generally ≤2 years {Keating et al 2002}, {Goy et al 2009}, {Hess et al 2009}, {Moskowitz et al 
2009}, {Di Bella et al 2010}, {Wierda et al 2010}, {Friedberg 2011}. Novel mechanisms of 
action are needed to offer additional treatment options for patients with lymphoid malignancies 
who are experiencing progressive lymphadenopathy or symptoms due to disease progression.
1.2.
Idelalisib
Idelalisib (Zydelig®) was first approved in the United States on July 23, 2014 for the treatment 
of relapsed CLL, follicular lymphoma (FL), and small lymphocytic lymphoma (SLL), followed 
by approval in the EU on September 18, 2014 (centrally authorized). To date, Zydelig is 
currently approved in 37 countries. Refer to local labeling for the approved indication 
statements.


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Idelalisib is a potent competitive inhibitor of the adenosine triphosphate (ATP) binding site of 
the phosphatidylinositol 3 kinase (PI3K) p110δ catalytic domain, which has been shown to be 
prominently expressed in cells of hematopoietic origin {Okkenhaug et al 2003}, 
{Vanhaesebroeck et al 2005}. The effects of p110δ on lymphocyte activation/function, cellular 
proliferation, and protection from apoptosis provide the rationale for targeting this isoform as a 
therapy for hematologic malignancies.
Further details on the preclinical pharmacology, toxicology, metabolism and pharmacokinetics 
(PK) of idelalisib can be found in the idelalisib Investigator’s Brochure (IB).
1.3.
Rationale for This Study
Study GS-US-315-0102 is being conducted to evaluate the safety and efficacy of GS-9820, a 
second generation PI3Kδ inhibitor in subjects with iNHL, DLBCL, MCL, HL, or CLL. GS-9820 
was anticipated to offer similar efficacy to idelalisib in lymphoid malignancies while offering a 
more favorable safety profile than idelalisib. The development of GS-9820 has been 
discontinued by Gilead Sciences due to demonstration of a similar safety profile to idelalisib. 
Manufacture of the investigational agent GS-9820 has been discontinued, and will no longer be 
available to the ongoing subjects in Study GS-US-315-0102.  
This rollover study provides access to idelalisib for eligible subjects receiving GS-9820 in Study 
GS-US-315-0102 at the time of study closure who have had objective evidence of clinical benefit 
defined as at least stable disease on imaging assessed by the independent review committee 
(IRC) and no toxicities prior to enrollment in this study that would preclude initiating therapy 
with idelalisib.  Subjects will be allowed to receive treatment on this study until unacceptable 
toxicity, progressive disease, study withdrawal, or death occurs.
1.4.
Benefit/Risk Assessment for the Study
Subjects enrolled in this study have a serious life-threatening disease, with limited treatment 
options. Without treatment their disease will progress and ultimately be fatal. Transitioning 
subjects from GS-9820 to idelalisib, a similar agent in class that has shown proof of clinical 
activity and has received regulatory approval for the treatment of relapsed CLL and iNHL 
{Gilead Sciences Limited 2015}, is rational as described in Section 1.3 of this protocol; 
therefore, subjects enrolled in this study may derive clinical benefit defined as an improvement 
in disease control such as response to study treatment. The risks that may accompany study 
treatment are related to the identified and potential toxicities of treatment with idelalisib and are 
described in Section 5 of this protocol and in the ICF. The management of these toxicities is 
described in Table 5-2. Taken together, there is a positive benefit/risk for initiating study 
treatment with idelalisib in subjects previously treated with GS-9820.
1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To provide idelalisib, a marketed PI3Kδ inhibitor, in lieu of GS-9820, an investigational 
second generation PI3Kδ inhibitor, to subjects receiving GS-9820 in Study GS-US-315-0102
at the time of study closure who have had objective evidence of clinical benefit defined as at 
least stable disease on imaging assessed by the IRC and no toxicities prior to enrollment in 
this study that would preclude initiating therapy with idelalisib. Idelalisib and GS-9820 are 
both in the class of agents that inhibit PI3Kδ and as such this exchange of class for class 
agent is warranted and acceptable.


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3.
STUDY DESIGN
3.1.
Endpoints
There is no primary endpoint of this study.
3.2.
Study Design
This study is an open-label, rollover study to provide idelalisib to subjects receiving GS-9820 in 
Study GS-US-315-0102 at the time of study closure.
3.3.
Study Treatments
All subjects will receive idelalisib 150 mg taken orally, twice per day (BID) continuously. 
3.4.
Duration of Treatment
Treatment will continue until unacceptable toxicity, disease progression, study discontinuation 
(outlined below), or death occurs.
3.5.
Discontinuation Criteria
A subject may be withdrawn from the study under the following circumstances:

The subject withdraws consent to participate in the study

The subject permanently discontinues idelalisib treatment for any reason

The subject experiences a toxicity that necessitates permanent discontinuation of idelalisib
treatment

The subject has progressive disease 

The subject does not comply with the requirements of the protocol (eg initiation of a 
non-protocol anti-tumor treatment)

Gilead, a regulatory agency, or an independent ethics committee (IEC) discontinues the study
The reason for withdrawal will be recorded in the eCRF.


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3.6.
Source Data
Electronic data (ie, diagnostic machines that transcribe data directly to a database, or data entered 
directly into an Electronic Medical Record system) is considered source data, provided the data 
is not recorded directly on the CRF/eCRF, and provided there is a clear audit trail in the 
electronic record(s). No data will be recorded directly on the CRF/eCRF, and any data recorded 
directly on the CRF/eCRF will not be considered source data.
3.7.
Biomarker Testing
There will be no biomarker testing in this study.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 6 subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure are anticipated.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Receiving GS-9820 in Study GS-US-315-0102 with objective evidence of clinical benefit 
defined as at least stable disease on imaging assessed by the IRC at the time of Study 
GS-US-315-0102 closure
2) For female subjects of childbearing potential, willingness to use a protocol recommended 
method of contraception during heterosexual intercourse from the signing of informed 
consent throughout the study treatment period and up to 30 days from the last dose of 
idelalisib (see Appendix 2)
3) For male subjects of reproductive potential having intercourse with females of childbearing 
potential, willing to use a protocol recommended method of contraception during 
heterosexual intercourse and to refrain from sperm donation throughout the study treatment 
period and for 90 days following discontinuation of idelalisib (see Appendix 2)
4) Willingness to comply with scheduled visits, drug administration plan, imaging studies, 
laboratory tests, other study procedures, and study restrictions. Note: Psychological, social, 
familial, or geographical factors that might preclude adequate study participation should be 
considered.
5) Evidence of a personally signed informed consent indicating that the subject is aware of the 
neoplastic nature  of their disease and has been informed of the procedures to be followed, 
the experimental nature of the therapy , alternatives, potential benefits, possible side effects, 
potential risks and discomforts, and other pertinent aspects of study participation.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not eligible to be enrolled in this 
study:
1) Known hypersensitivity or intolerance to any of the active substances or excipients in the 
formulation of idelalisib.


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2) Toxicities that would preclude initiating therapy with idelalisib prior to enrollment
(eg history of drug-induced pneumonitis, ongoing inflammatory bowel disease)
3) Concurrent participation in another therapeutic clinical trial.
4) Pregnant or breastfeeding.


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5. 
INVESTIGATIONAL MEDICINAL PRODUCTS 
5.1. 
Randomization, Blinding and Treatment Codes 
The study is open-label and non-randomized. 
5.2. 
Description and Handling of Study Treatments 
5.2.1. 
Formulation 
Final 
Original 
Idelalisib 150 mg tablets are pink, oval-shaped and debossed with ' 'GSI' ' on one side and 
" 150" on the other. The 100 mg tablets are orange, oval-shaped and debossed with " GSI" on 
one side and " 1 00" on the other. All tablets are film-coated, and include the followina inactive 
exci ients: PD 
5.2.2. 
Packaging and Labeling 
Idelalisib tablets, 150 mg or 100 mg, are packaged in white, high density polyethylene (HDPE) 
bottles. Each bottle contains 60 tablets and polyester packing material. Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an induction-
sealed and alumimun-faced liner. 
Idelalisib to be distributed to centers in the US and other pruticipating cmmtries shall be labeled 
to meet applicable requirements of the United States Food and Dmg Administration (FDA), EU 
Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal Products), 
and/or other local regulations. 
5.2.3. 
Storage and Handling 
Idelalisib should be stored at controlled room temperature of 25°C (77°F); excursious ru·e 
permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the 
label. Until dispensed to the subjects, all bottles of study <hugs should be stored in a securely 
locked ru·ea, accessible only to authorized site personnel. 
To ensure the stability and proper identification, study <hug should not be stored in a container 
other than the container in which they were supplied. Consideration should be given to handling, 
preparation, and disposal through measures that minimize <h·ug contact with the body. 
Appropriate precautions should be followed to avoid direct eye contact or exposure when 
handling. 
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5.2.4.
Dosage and Administration of Idelalisib
Idelalisib formulated drug product of 100 and 150 mg strengths has been manufactured for 
clinical trials and will be provided to the subject to be taken at home. Subjects should be 
instructed to take the doses with water. Idelalisib may be taken with or without food. Missed 
doses should not be taken unless it is within 6 hours of the scheduled dosing and vomited doses 
should be retaken only if the tablet is visible in the vomitus.
Idelalisib will be taken twice daily. Idelalisib should be taken at approximately the same times 
each day. Ideally, doses should be taken at approximately 12 hour intervals as instructed 
(eg, at 7 AM and at 7 PM). While it is realized that variations in dosing schedule may occur in 
the outpatient setting, the prescribed regimen should be followed as closely as possible.
5.2.5.
Dispensing
The clinic staff (eg, pharmacist or other qualified person) will be responsible for dispensing 
idelalisib. It is planned that idelalisib will be dispensed at 4-week intervals through the 
first 16 weeks of treatment, at 8-weeks, and at 12-week intervals thereafter. Sufficient idelalisib
will be provided for each study period at the beginning of the period. Tablets should be 
dispensed in the original bottles provided.
The clinic staff (eg, pharmacist or other qualified person) will write the subject number on each 
bottle that is dispensed. Immediately before dispensing, the clinic staff will write the bottle 
number for each dispensed bottle in the idelalisib administration record corresponding to the 
subject number.
5.2.6.
Premedication
No specific pre-medications or supporting medications are required in conjunction with idelalisib
administration.
5.2.7.
Administration Instructions
The prescribed dose of idelalisib should be taken orally. At each dose administration, the tablet 
number corresponding to the appropriate dose of idelalisib is to be swallowed whole with 
100 to 200 mL (~4 to 8 ounces) of water. In case of breakage of the tablets in the oral cavity, 
additional water should be taken as a rinse.
Idelalisib may be taken with or without food. There are no known dietary restrictions related to 
idelalisib use.
5.2.8.
Dosing Schedule
Idelalisib will be administered on a BID schedule. Idelalisib should be taken at approximately the 
same times each day.


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5.2.9.
Dose Levels
Idelalisib dose levels are shown in Table 5-1. The starting dose level will be 150 mg BID. The 
lower dose level (Dose Level -1) is provided in case a subject requires a dose modification.
Table 5-1.
Idelalisib Dose Levels
Dose Level
Dosing Regimen
Starting
150 mg BID
-1
100 mg BID
Abbreviation: BID=twice per day
Consistent with Table 5-2, if a subject experiences an AE that is suspected to be related to 
idelalisib during the course of study, idelalisib administration may be held, as necessary, until the 
AE resolves or stabilizes to an acceptable degree (as defined in Table 5-2). Thereafter, idelalisib 
may be reinitiated at either the Starting Dose Level or at Dose Level -1 consistent with the 
instructions in Section 5.2.10. A further attempt at reinitiation of therapy at Dose Level -1 may 
be attempted if the investigator feels that a second rechallenge at that dose level is medically 
appropriate. If the subject cannot tolerate idelalisib after 2 rechallenges at Dose Level -1 for the 
same AE, then the subject should be discontinued from idelalisib treatment.
After an idelalisib dose reduction, the dose need not be re-escalated, even if there is minimal or 
no toxicity with the reduced dose. However, if the subject tolerates Dose Level -1 of idelalisib
for 4 weeks, then the dose may be increased back to Starting Dose Level, at the discretion of 
the investigator. Such a re-escalation may be particularly warranted if further evaluation reveals 
that the AE that led to the dose reduction was not related to idelalisib.
5.2.10.
Idelalisib Dose Adjustments
The dose adjustment recommendations in Table 5-2 are based on the Common Terminology 
Criteria for Adverse Events (CTCAE) grade of specific toxicities. However, exceptions are 
expected for subjects who initiate study treatment with low blood counts. Clinical judgment 
should apply, and in cases of uncertainty, the study medical monitor should be contacted.
The dose modification instructions focus on the types of events most commonly attributed to 
idelalisib. The recommendations provided in Table 5-2 comprise only guidelines; variations from 
these recommendations may be warranted based on an investigator’s individual judgment in 
considering potential risks, benefits, and therapeutic alternatives available to each subject.


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Table 5-2.
Dose Adjustment Guidelines {Gilead Sciences Inc 2014}
Pneumonitis
Any symptomatic pneumonitis
Discontinue Zydelig in subjects with any severity of symptomatic pneumonitis
ALT/AST
>3-5 x ULN
>5-20 x ULN
>20 x ULN
Maintain idelalisib dose. 
Monitor at least weekly 
until <1 x ULN.
Withhold idelalisib.
Monitor at least weekly until 
ALT/AST are <1 x ULN, 
then may resume idelalisib at 
100 mg BID.
Discontinue idelalisib 
permanently.
Bilirubin
>1.5-3 x ULN
>3-10 x ULN
>10 x ULN
Maintain idelalisib dose. 
Monitor at least weekly 
until <1 x ULN.
Withhold idelalisib. 
Monitor at least weekly 
until bilirubin is <1 x ULN, 
then may resume idelalisib 
at 100 mg BID.
Discontinue idelalisib 
permanently.
Diarrhea
Moderate diarrhea
Severe diarrhea or 
hospitalization
Life-threatening diarrhea
Maintain idelalisib dose. 
Monitor at least weekly 
until resolved.
Withhold idelalisib. 
Monitor at least weekly 
until resolved, then may 
resume idelalisib at 100 mg 
BID.
Discontinue idelalisib 
permanently.
Neutropenia
ANC 1.0 to <1.5 Gi/L
ANC 0.5 to <1.0 Gi/L
ANC <0.5 Gi/L
Maintain idelalisib dose.
Maintain idelalisib dose. 
Monitor ANC at least 
weekly.
Interrupt idelalisib. Monitor 
ANC at least weekly until 
ANC ≥0.5 Gi/L, then may 
resume idelalisib at 100 mg 
BID.
Thrombocytopenia
Platelets 50 to <75 Gi/L
Platelets 25 to <50 Gi/L
Platelets <25 Gi/L
Maintain idelalisib dose.
Maintain idelalisib dose. 
Monitor platelet counts at 
least weekly.
Interrupt idelalisib. Monitor 
platelet count at least weekly. 
May resume idelalisib at 
100 mg BID when platelets 
≥25 Gi/L.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ULN, upper limit of normal
5.3.
Prior and Concomitant Medications
If considered necessary for the subject’s well-being, drugs for concomitant medical conditions or 
for symptom management may be given at the discretion of the investigator.


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Any concomitant medications prescribed as a therapeutic intervention for or resulting in an AE 
or SAE during the course of the study and the reason for use should be recorded on the eCRFs. 
5.3.1. 
Anticancer or Experimental Therapies Other than Investigational 
Treatments 
Except for corticosteroids, no other anticancer therapies (including chemotherapy, radiation, 
antibody therapy, immunotherapy, or other experimental therapies) of any kind are permitted. 
Subjects are not allowed to participate concurrently in any other therapeutic clinical study. 
5.3.2. 
Antibiotics 
Except in a subject who has a contra-indication, investigators should consider initiation of 
antibiotic prophylaxis against pneumocystis infection ( eg, with trimethoprim-sulfamethoxazole, 
dapsone, aerosolized pentamidine, or atovaquone) beginning prior to idelalisib administration. 
Investigator discretion and local practices or guidelines may be followed. 
For subjects who develop an infection, appropriate medical therapy (with antibiotics, antifungals, 
or antiviral) or other interventions should be instituted. Whenever appropriate, subjects may 
continue with idelalisib during treatment for the infection. 
5.3.3. 
Antidiarrheals 
As needed, subjects may be prescribed loperamide (Imodium® or others) or diphenoxylate and 
atropine (Lomotil®) to control diarrheal symptoms. 
5.3.4. 
Corticosteroids 
Subjects may receive topical, inhaled, enteric, or systemic corticosteroids while on study. 
5.3.5. 
Granulocyte Colony-Stimulating Factors and Erythropoietin 
Granulocyte-macrophage colony-stimulating factor (GM-CSF) should not be administered given 
the potential for GM-CSF-related inflammatory symptoms. 
G-CSF (filgrastim, PEG-filgrastim, lenograstim) may be administered in response to 
Grade 4 neutropenia or neutropenic complications; (see Table 5-2). 
While erythropoietic agents (eg, erythropoietin or darbepoetin) may be administered for 
Grade ~3 anemia, their use in this study is discouraged given the potential to confound 
assessments of improvements in bone marrow function related to idelalisib. 
5.3.6. 
Drugs that Alter CYP3A-Dependent Metabolism 
Idelalisib is metabolized to its major metabolite -PO 
via aldehyde oxidase and 
cytochrome P450 3A (CYP3A). Idelalisib also undergoes minor metabolism by UDP 
glucoronosyltransferase 1-4 (UGT1A4). The AUC ofidelalisib was increased 1.8 fold when 
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idelalisib was coadministered with a strong CYP3A inhibitor. Therefore, if subjects are taking 
concomitant strong CYP3A inhibitors, the subject should be monitored closely for signs of 
idelalisib toxicity and the dose modifications for adverse reactions should be followed in the 
event of toxicity (see Table 5-2). 
Additionally, idelalisib exposures are approximately 75% lower when coadministered with 
rifampin, a highly potent inducer of CYP3A. Therefore, avoid coadministration of strong 
inducers ofCYP3A (rifampin, carbamazepine, phenytoin, and St. John's wort) with idelalisib. 
5.3.7. 
Drugs that undergo CYP3A-Dependent Metabolism 
The major metabolite of idelalisib, PPD 
is a reversible and time dependent inhibitor of 
CYP3A; accordingly, coadministration of idelalisib with midazolam, a probe CYP3A substrate, 
resulted in a ~5-fold increase in midazolam systemic exposure (AUC). Coadministration of 
drugs that are narrow therapeutic index CYP3A substrates with idelalisib may result in an 
increase in their systemic exposures ( eg, antiarrhythmics, calcium channel blockers, 
benzodiazepines, certain HMG-CoA reductase inhibitors, phosphodiesterase-S [PDE5] 
inhibitors, warfarin). Avoid coadministration of drugs that are narrow therapeutic index CYP3A 
substrates ( eg, alfentanil, cyclosporine, sirolimus, tacrolimus, cisapride, pimozide, fentanyl, 
quinidine, ergotamine, dihydroergotamine, astemizole, terfenadine) with idelalisib. 
5.3.8. 
Immunization 
Because of its actions to inhibit PI3K8-dependent B-cell function, high doses of idelalisib can 
impair primary or secondary responses to immunization in animals. 
The specific clinical relevance ofthese findings with idelalisib is unknown. However, for 
subjects who are at substantial risk of an infection ( eg, influenza) that might be prevented by 
immunization, consideration should be given to providing the vaccine prior to initiation of study 
therapy. 
Of note, the safety of immunization with live viral vaccines following idelalisib therapy has not 
been studied and vaccination with live virus vaccines during study treatment is not 
recommended. 
5.3.9. 
Ultraviolet Exposure 
While nonclinical findings suggest the hypothetical potential for phototoxicity in humans, 
available clinical data do not reveal a photosafety concern. Although specific clinical correlates 
for these nonclinical data are not available, investigators and study subjects should be observant 
for the possibility that study participants may have exaggerated sunburn reactions ( eg, burning, 
erythema, exudation, vesicles, blistering, edema) involving areas of skin exposed to ultraviolet 
light. 
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5.3.10.
Surgery
There are no known effects of idelalisib on coagulation or wound healing. Pending receipt of 
additional information and considering the subject’s current platelet counts, idelalisib may be 
continued in the peri-procedural period in subjects who require surgery or invasive procedures.
5.4.
Accountability for Idelalisib
The disposition of all idelalisib should be documented from the time of receipt at the site through 
subject dispensing and return.
Study personnel must ensure that idelalisib is kept in a secure locked area with access limited to 
authorized personnel. The idelalisib must not be used outside the context of this protocol. Under 
no circumstances should the investigator or site personnel supply idelalisib to other investigators 
or clinics, or allow the idelalisib to be used other than as directed by this protocol.
The investigator and/or the responsible site personnel must maintain accurate records of the 
receipt of idelalisib shipped by Gilead Sciences or its designee, including, but not limited to, the 
date received, lot number, amount received, and the disposition of all idelalisib. Upon receipt of 
a drug shipment, the shipment must be logged into the idelalisib accountability records, these 
records must also be maintained to include the subject number to whom the idelalisib was 
dispensed and the date, quantity and lot number of the idelalisib dispensed.
Depending upon the decision of Gilead Sciences, remaining unused idelalisib supply will be 
returned to Gilead Sciences or its designee after the study is completed or will be discarded or 
destroyed at the clinical site. If the idelalisib is discarded or destroyed at the clinical site, 
standard institutional policy should be followed. Records documenting the date of idelalisib
shipping or destruction, relevant lot numbers, and amount shipped or destroyed should be 
maintained.
5.4.1.
Overdose Precautions
In Phase 1 studies, an MTD for idelalisib was not reached when administering the drug 
continuously at dose levels of 350 mg/dose BID (700 mg per day) {Coutre et al 2011}, {Kahl et 
al 2011}. However, in this protocol, an overdose is defined as administration of more than the 
prescribed daily dose (ie, >300 mg in a single day).
The Gilead Sciences medical monitor should be contacted if an idelalisib overdose occurs. Cases 
of idelalisib overdose will result in specific reporting requirements.
5.4.2.
Inadvertent Exposure and Spill Precautions
Based on available data from nonclinical studies, idelalisib does not appear to be acutely toxic, 
genotoxic, or irritative at levels that are likely to result from inadvertent exposure to the contents 
of broken tablets. However, personnel handling the drug should use reasonable precautions to 
avoid eye contact, skin contact, inhalation, or ingestion of the idelalisib product. For further 
information regarding inadvertent exposure and spill precautions, please consult the idelalisib
investigator brochure.


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5.4.3.
Investigational Medicinal Product Return or Disposal
Subjects will be instructed to return any unused idelalisib in the original container at post 
treatment study visits. Returned medication will be reconciled by the investigator in order to 
monitor the subject’s compliance with the medication regimen. When possible, all idelalisib
returned by the subject should be retained for review by the study site monitor prior to return to 
Gilead Sciences or destruction.
5.5.
Discontinuation from Study
Subject study participation may be ended due to any of the follow reasons:

Withdrawal of consent

Objective evidence of disease progression.

Unacceptable toxicity or unable to tolerate a second rechallenge for the same AE.

Any subject who becomes pregnant or begins breastfeeding.

Initiation of non-protocol specfied anticancer therapy.

Noncompliance with idelalisib administration, study procedures, or study requirements.

The investigator may discontinue idelalisib, if it is not in the subject’s best interest to 
continue.

Any subject who is lost to follow-up.

Death

Discontinuation of study by the Sponsor, a regulatory agency, or an EC


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Table 6-1 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment 
6.1.1.
Subject Recruitment
This study will enroll subjects receiving GS-9820 in Study GS-US-315-0102 at the time of study 
closure who have had objective evidence of clinical benefit defined as at least stable disease on 
imaging assessed by the IRC and no toxicities prior to enrollment in this study that would
preclude initiating therapy with idelalisib. The study sponsor will post a description of the study 
on the ClinicalTrials.gov website.
6.1.2.
Subject Compensation for Participation
Subjects will not be paid for participation in the study other than medical care that may be 
provided. Payments for such items as lost wages, disability, discomfort due to injury, or meals 
obtained while waiting at the clinical research center will not be provided. Through the informed 
consent process, study candidates will be notified that their insurance company could be charged 
for standard care that is a component of this research study and that subjects may be responsible 
for co-payments and deductible payments that are typical for their insurance coverage.
6.1.3.
Screening Visit
The investigator must inform each prospective subject of the nature of the study, explain the 
potential risks, and obtain written informed consent from the subject and/or a legal guardian 
prior to performing any study-related screening procedures. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (CRF/eCRF).  
All other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history CRF/eCRF.  
See Section 7 Adverse Events and Toxicity Management for additional details.
6.2.
Treatment Assessments
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all SAEs, as well as any non-serious all grade AEs on the AE case 
report form (eCRF). All other untoward medical occurrences observed during the screening 


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period, including exacerbation or changes in pre-existing conditions are considered medical 
history (not collected for this study). See Adverse Events and Toxicity Management (Section 7) 
for additional details.
While on study, the subject will return at regular intervals for the following procedures:

Evaluation of disease status per standard of care

Laboratory lab tests (ALT/AST/total bilirubin)

Recording of all grade AEs and all SAEs

Return of used drug supplies and dispensing of new idelalisib supply
The specific study procedures to be conducted for each subject enrolled in the study are 
presented in Table 7-1 and are described in the sections that follow.
6.2.1.
Clinical Evaluation
While on study, the subject will be followed for disease status according to standard of care. At 
each study visit the subject’s disease status will be assessed. If no change in disease status is 
identified and the subject is dispensed additional idelalisib, the most recent prior response 
documented for the study will be recorded.
6.3.
End of Study
Subjects will be withdrawn from this study if they develop progressive disease, unacceptable 
toxicity related to idelalisib, withdraw consent, are noncompliant, or are lost to follow up or die. 
In this event, the following procedures should be performed:

Return of used and unused drug supply

Recording of all Grade AEs and all SAEs

Investigator Response Assessment

Recording of the reason for withdrawal

Deaths occurring within 30 days following the last dose of idelalisib, even if occurring after 
the End of Study Visit, will be captured.


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Table 6-1.
Schedule of Study Procedures
Period
Screen
Treatment
Visit
1
2
3
4
5
6
7
8+
End of
study
Week
-4
0
4
8
12
16
24
Q12 
weeks
Study Day
Within
-28 days
1
28
52
84
112
168
Visit Window
±2
±2
±2
±2
±2
±7
Informed consent
X
Serum -HCGa
X
ALT/AST/total bilirubin
X
X
X
X
X
X
X
X
X
Urine pregnancy testa
X
X
X
X
X
X
X
X
Assess adverse events and SAEs
X
X
X
X
X
X
X
X
Record concomitant medicationsb
X
X
X
X
X
X
X
X
Idelalisib dispensing/accounting
X
X
X
X
X
X
X
X
Investigator response assessmentc
X
X
X
X
X
X
X
X
a
For women of child bearing potential; Serum -HCG to be collected to be collected at screening, urine pregnancy test to be 
collected at visits from first dose of idelalisib to EOS
b
Concomitant medications only collected if it is related to an AE
c
Record investigator response assessment if obtained per standard of care
Abbreviations: -HCG=beta human chorionic gonadotropin, ALT=alanine aminotransferase, AST=aspartate aminotransferase


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Lymphocytosis

Laboratory abnormalities not requiring clinical intervention or further investigation. Such 
abnormalities will be captured as part of overall laboratory monitoring.

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
CRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)


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
In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to idelalisib interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Idelalisib and Procedures
The investigator or qualified sub-investigator is responsible for assessing the relationship to 
idelalisib therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than idelalisib. For 
SAEs, an alternative causality must be provided (eg, pre-existing condition, underlying 
disease, intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.


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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg., venipuncture)
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the CTCAE, Version 4.03 and available at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or 
Grade 5 (fatal) to describe the maximum intensity of the adverse event. For purposes of 
consistency with the CTCAE, these intensity grades are defined in Table 7-1.
Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Sign or symptom is present, but it is easily tolerated, is not expected to have a 
clinically significant effect on the subject’s overall health and well-being, does 
not interfere with the subject’s usual function, and is not likely to require 
medical attention.
Grade 2
Moderate
Sign or symptom causes interference with usual activity or affect clinical status, 
and may require medical intervention.
Grade 3
Severe
Sign or symptom is incapacitating or significantly affects clinical status and 
likely requires medical intervention and/or close follow-up.
Grade 4
Life-threatening
Sign or symptom results in a potential threat to life.
Grade 5
Fatal
Sign or symptom results in death.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events listed in Section 7.1.2.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
All SAEs, regardless of cause or relationship, that occur after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 


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eCRF database and Gilead Drug Safety and Public Health (DSPH) or designee as instructed. 
This also includes any SAEs resulting from protocol-associated procedures performed from 
screening onwards.
All AEs, regardless of cause or relationship, that occur from initiation of study medication until 
30 days after last administration of idelalisib must be reported to the eCRF database as 
instructed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of idelalisib, regardless of causality, should also be reported.
All AEs should be followed up until resolution if possible. If by the last day on study (including 
the off-study medication follow-up period) the AE has not resolved, then the AE will be 
followed up until the investigator and/or Gilead Sciences determine that the subject's condition is 
stable. However, Gilead Sciences may request that certain AEs be followed until resolution.
Investigators are not obligated to actively seek SAEs after the 30 day period. However, if the 
investigator learns of any SAEs that occur after study participation has concluded and the event 
is deemed relevant to the use of idelalisib, he/she should promptly document and report the event 
to Gilead DSPH or designee as instructed.
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guidelines.
7.3.1.
Serious Adverse Event (eSAE) Reporting Process 
Site personnel record the SAE on the paper serious adverse event reporting form and submit via 
fax to Gilead DSPH within 24 hours.
All AEs and SAEs will be recorded in the CRF/eCRF database within the timelines outlined in 
the CRF/eCRF completion guideline.
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
Additional information may be requested to ensure the timely completion of accurate safety 
reports.
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/eCRF and the event description section of the SAE 
form.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 


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worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with idelalisib. The investigator should notify the IEC of SUSAR reports as soon as is practical, 
where this is required by local regulatory agencies, and in accordance with the local institutional 
policy. 
7.4.1.
Reporting of Adverse Events Relating and Other Anticipated Medical Events 
in the Study Population
Given the endpoints of the study and in order to maintain the integrity of the study, the following 
events that are assessed as unrelated to idelalisib will not be considered SAEs:

Progression of lymphoid malignancy

Death related to progression of lymphoid malignancy

Disease progression and death from disease progression should be reported as SAEs by the 
investigator only if it is assessed that the idelalisib caused or contributed to the disease 
progression (ie, by a means other than lack of effect).  Unrelated disease progression should 
be captured on the eCRF.
These will be reported, as appropriate, in the final clinical study report and in any relevant 
aggregate safety reports.
7.4.2.
Toxicity Management 
See Table 5-2 for more information related to recommended dose modifications associated with 
toxicities. Please refer to the current idelalisib IB for information related to toxicity management.
7.5.
Special Situations Reports
7.5.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.


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Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
7.5.2.
Instructions for Reporting Special Situations
7.5.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study to the Gilead DSPH using the pregnancy 
report form within 24 hours of becoming aware of the pregnancy.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post 
study must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH  using the pregnancy outcome 
report form. If the end of the pregnancy occurs after the study has been completed, the outcome 
should be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: 
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477. 
Pregnancies of female partners of male study subjects exposed to idelalisib must also be reported 
and relevant information should be submitted to Gilead DSPH using the pregnancy and 
pregnancy outcome forms within 24 hours. Monitoring of the subject should continue until the 
conclusion of the pregnancy. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead DSPH, fax number +1 650 522-5477
or email Safety_FC@gilead.com. 


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Refer to Appendix 2 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.5.2.2.
Reporting Other Special Situations
All other special situation reports (excluding pregnancy) must be reported on the special 
situations report form and forwarded to Gilead DSPH within 24 hours of the investigator 
becoming aware of the situation. These reports must consist of situations that involve idelalisib, 
but do not apply to concomitant medications. Except for situations that result in AEs, special 
situations involving concomitant medication will not be reported. Any inappropriate use of 
concomitant medications prohibited by this protocol should not be reported as “misuse,” but may 
be more appropriately documented as a protocol deviation.
Refer to the CRF/eCRF completion guidelines for full instructions on the mechanism of special 
situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE CRF/eCRF and/or the SAE report form. Details of the symptoms 
and signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives
As noted in Section 2, the primary objective is to provide idelalisib to subjects receiving
GS-9820 in Study GS-US-315-0102 at the time of study closure who have had objective 
evidence of clinical benefit defined as at least stable disease on imaging assessed by the IRC and 
no toxicities prior to enrollment in this study that would preclude initiating therapy with 
idelalisib.
8.2.
Safety Endpoints
Safety will be assessed with endpoints including incidence of ≥Grade 3 AEs, SAEs, and deaths.
8.3.
Analysis Sets
Both safety and efficacy will be assessed using data collected from subjects who received at least 
1 dose of idelalisib.
8.4.
Analysis Methods
All the analyses will be limited to descriptive summaries and listings. Categorical variables will 
be summarized with the number and percentage of subjects in each category. Continuous 
variables will be summarized by presenting n, mean, standard deviation, median, Q1, Q3, 
minimum and maximum.
8.5.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable sub-investigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any sub-investigator’s) participation in the study. The investigator and 
sub-investigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Independent Ethics Committee (IEC) Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IEC. The investigator will not begin any study subject activities until 
approval from the IEC has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IEC any modifications made to the protocol or any accompanying material to be provided to 
the subject after initial IEC approval, with the exception of those necessary to reduce immediate 
risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IEC-approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately signed 


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and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IEC or local 
requirements. 
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form submitted to the Sponsor. NOTE: The investigator must keep a screening log showing 
codes, names, and addresses for all subjects screened and for all subjects enrolled in the trial.
Subject data will be processed in accordance with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, CRF/eCRF, idelalisib, and any other study information, 
remain the sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IEC
and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);
Birth dates will be collected as per local regulatory requirements, as needed

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);


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
Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of idelalisib, including dates of dispensing and 
return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data. The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 
data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), the investigator will use his/her log in 
credentials to confirm that the forms have been reviewed, and that the entries accurately reflect 
the information in the source documents. The eCRF capture the data required per the protocol 


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schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (eg data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Drug Accountability and Return
Gilead recommends that used and unused idelalisib supplies be returned to the shipping facility 
from which it came for eventual destruction. The study monitor will provide instructions for 
return. If return is not possible, the study monitor will evaluate each study center’s disposal 
procedures and provide appropriate instruction for destruction of unused idelalisib supplies. If 
the site has an appropriate standard operating procedure (SOP) for drug destruction as 
determined by Gilead QA, the site may destroy used (empty or partially empty) and unused 
idelalisib supplies in accordance with that site’s approved SOP. A copy of the site’s approved 
SOP will be obtained for central files. 
If idelalisib is destroyed on site, the investigator must maintain accurate records for all idelalisib
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the idelalisib. Upon study completion, copies of 
the idelalisib accountability records must be filed at the site. Another copy will be returned to 
Gilead.
The study monitor will review idelalisib supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to appropriately qualified personnel from Gilead Sciences or 
its representatives, to IECs, or to regulatory authority or health authority inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IEC in 
accordance with local requirements and receive documented IEC approval before modifications 
can be implemented.


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9.2.2.
Communications with Regulatory Authorities
Gilead Sciences, working either directly or through designees, will assume responsibility for 
regulatory interactions with relevant regulatory authorities. Gilead Sciences will maintain an 
IND for idelalisib in support of the study in the United States and will maintain similar 
regulatory applications with other regulatory authorities, as required for conduct of the study. In 
fulfilling this responsibility, Gilead Sciences (or a designee) will collect, assemble, and 
communicate all required regulatory documents (eg, Form FDA 1572, investigator financial 
disclosure forms, protocol and protocol amendments, investigator brochures, informed consent 
documents, annual reports) as required by regulation. Gilead Sciences (or a designee) will also 
assume responsibility for adverse event reporting to regulatory authorities as described in 
Section 7.4.
9.2.3.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). Gilead 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly 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.
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg attendance at Investigator's Meetings.  If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
CRF/eCRF.
The monitor is responsible for routine review of the CRF/eCRF at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the CRF/eCRF. The investigator agrees to cooperate with the monitor to 
ensure that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies) and IECs. In terminating the study, Gilead and the investigator will 
assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
Coutre S, Byrd J, Furman R, Brown J, et al. Phase I study of CAL-101, an isoform-selective 
inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously 
treated chronic lymphocytic leukemia [Abstract]. 47th Annual Meeting of the 
American Society of Clinical Oncology (ASCO); 2011 June 3; Chicago, IL. 
Di Bella N, Taetle R, Kolibaba K, Boyd T, Raju R, Barrera D, et al. Results of a phase 2 study of 
bortezomib in patients with relapsed or refractory indolent lymphoma. Blood 
2010;115 (3):475-80.
Diehl V, Thomas RK, Re D. Part II: Hodgkin's lymphoma--diagnosis and treatment. Lancet 
Oncol 2004;5 (1):19-26.
Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia. Lancet 2008;371 (9617):1017-29.
Eichhorst B, Hallek M, Dreyling M. Chronic lymphocytic leukaemia: ESMO Clinical Practice 
Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21 Suppl 
5:v162-4.
Friedberg JW. New strategies in diffuse large B-cell lymphoma: translating findings from gene 
expression analyses into clinical practice. Clin Cancer Res 2011;17 (19):6112-7.
Gilead Sciences Inc. ZYDELIG® (idelalisib) tablets, for oral use. U.S. Prescribing Information. 
Foster City, CA. July 2014:
Gilead Sciences Limited. Zedelig (idelalisib) 150mg. Summary of Product Characteristics. 
Cambridge,United Kingdom. Revised  21 July.  2015:
Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Bortezomib in 
patients with relapsed or refractory mantle cell lymphoma: updated time-to-event 
analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 2009;20 
(3):520-5.
Gribben JG, O'Brien S. Update on therapy of chronic lymphocytic leukemia. J Clin Oncol 
2011;29 (5):544-50.
Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of 
rituximab to fludarabine and cyclophosphamide in patients with chronic 
lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376 
(9747):1164-74.


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Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, et al. Phase III study 
to evaluate temsirolimus compared with investigator's choice therapy for the 
treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27 
(23):3822-9.
Hoppe RT, Advani RH, Ambinder RF, Bierman PJ, Bloomfield CD, Blum K, et al. Hodgkin 
disease/lymphoma. J Natl Compr Canc Netw 2008;6 (6):594-622.
Jost L. Hodgkin's disease: ESMO clinical recommendations for diagnosis, treatment and follow-
up. Ann Oncol 2007;18 (Suppl 2):ii53-4.
Kahl B, Byrd J, Flinn I, Wagner-Johnston N, Spurgeon S, al E. Significant Clinical Activity Of 
Cal-101, An Isoform-Selective Inhibitor Of Phosphatidylinositol 3 Kinase P110D, 
In Patients With Relapsed Or Refractory Indolent And Mantle Cell Lymphoma 
[Abstract 350] 11th Triennial International Conference on malignant Lymphoma 
(Icml). Lugano, Swizterland: 2011:
Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, et al. Therapeutic role of alemtuzumab 
(Campath-1H) in patients who have failed fludarabine: results of a large 
international study. Blood 2002;99 (10):3554-61.
Kuruvilla J. Standard therapy of advanced Hodgkin lymphoma. Hematology / the Education 
Program of the American Society of Hematology. American Society of 
Hematology 2009:497-506.
Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B, et al. Immunochemotherapy 
with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone 
significantly improves response and time to treatment failure, but not long-term 
outcome in patients with previously untreated mantle cell lymphoma: results of a 
prospective randomized trial of the German Low Grade Lymphoma Study Group 
(GLSG). J Clin Oncol 2005;23 (9):1984-92.
Moskowitz AJ, Perales MA, Kewalramani T, Yahalom J, Castro-Malaspina H, Zhang Z, et al. 
Outcomes for patients who fail high dose chemoradiotherapy and autologous stem 
cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J 
Haematol 2009;146 (2):158-63.
Okkenhaug K, Vanhaesebroeck B. PI3K-signalling in B- and T-cells: insights from gene-
targeted mice. Biochemical Society transactions 2003;31 (Pt 1):270-4.
Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, et al. Intensified 
chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab 
for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label 
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Salles GA. Clinical features, prognosis and treatment of follicular lymphoma. Hematology / the 
Education Program of the American Society of Hematology. American Society of 
Hematology 2007:216-25.
Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, et al. Long-term results of 
combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority 
of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol 1987;5 
(1):27-37.
Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T, et al. Immunochemotherapy with 
rituximab and overall survival in patients with indolent or mantle cell lymphoma: 
a systematic review and meta-analysis. J Natl Cancer Inst 2007;99 (9):706-14.
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Lymphocytic Leukemia. Available at: 
http://seer.cancer.gov/statfacts/html/clyl.html. Accessed 12 May 2011.
Vanhaesebroeck B, Ali K, Bilancio A, Geering B, Foukas LC. Signalling by PI3K isoforms: 
insights from gene-targeted mice. Trends Biochem Sci 2005;30 (4):194-204.
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as single-agent CD20 immunotherapy in fludarabine-refractory chronic 
lymphocytic leukemia. J Clin Oncol 2010;28 (10):1749-55.
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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
199 EAST BLAJNE STREET 
SEATTLE, WA 98102 
STUDY ACKNOWLEDGEMENT 
An Open Label, Roll Over Study to Provide Idelalisib to Subjects Previously Treated with 
the Investigational PI3Ko Inhibitor, GS-9820 
Original Protocol GS-US-313-2120, 05 January 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
po-------------------. 
Lyndah Dreiling, MD 
Gilead Medical Monitor 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains aJI necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I wiU provide aJl study personnel under my supervision copies of the protocol and access to aU 
information provided by Gilead Sciences, Inc. 1 will discuss this material with them to ensure 
that tbey are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTW. 
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Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a) Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause.  In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b) Definition of Male Fertility
For the purposes of this study, a male born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Idelalisib has insufficient data to exclude the possibility of a clinically relevant interaction with 
hormonal contraception that results in reduced contraception efficacy.  Therefore, contraceptive 
steroids are not recommended as a contraceptive method either solely or as a part of a 
contraceptive regimen.  Data from clinical pharmacokinetic interaction studies of idelalisib have 
demonstrated no adverse effect on fertility or embryo-fetal development.  However, there is no 
clinical data of idelalisib in pregnant women.  Please refer to the latest version of the 
investigator’s brochure for additional information. 
b) Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires using at least an acceptable 
effective contraceptive measure.  They must also not rely on hormone-containing contraceptives 
as a form of birth control during the study.  They must have a negative serum pregnancy test at 
Screening and a negative pregnancy test on the Baseline/Day 1 visit prior to randomization.  At 
minimum, a pregnancy test will be performed at the end of relevant systemic exposure.  In the 


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event of a delayed menstrual period (over one month between menstruations), a pregnancy test 
must be performed to rule out pregnancy.  This is even true for women of childbearing potential 
with infrequent or irregular periods.  They must also agree to one of the following from 
Screening until 30 days after the end of relevant systemic exposure.
Complete abstinence from intercourse of reproductive potential.  Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual lifestyle.
Or
Consistent and correct use of 1 of the following methods of birth control listed below. 

Intrauterine device (IUD) with a failure rate of <1% per year

Tubal sterilization

Ensure micro-insert system (provided confirmation of success 3 months after procedure)

Vasectomy in the male partner (provided that the partner is the sole sexual partner and had 
confirmation of surgical success 3 months after procedure)

Barrier methods (one female barrier and one male barrier must be used in combination)
Female barriers: Diaphragm with spermicide or Cervical cap with spermicide
Male barriers: Male condom (with or without spermicide)
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 30 days after the end of relevant systemic exposure
3) Contraception Requirements for Male Subjects
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment until the end of relevant 
systemic exposure.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM).  Female condom and male condom should not be used 
together.


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5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last idelalisib dose. Subjects who become 
pregnant or who suspect that they are pregnant during the study must report the information to 
the investigator and discontinue idelalisib immediately. Subjects whose partner has become 
pregnant or suspects she is pregnant during the study must report the information to the 
investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome 
are outlined in Section 7.5.2.1.