An Extension Study to Investigate the Safety and Durability of Clinical Activity of Idelalisib in Subjects With Hematologic Malignancies
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia, Lymphoma, Non-Hodgkin
Sponsor: Gilead Sciences

CLINICAL STUDY PROTOCOL
Study Title:
An Extension Study to Investigate the Safety and Durability 
of Clinical Activity of Idelalisib in Subjects with 
Hematologic Malignancies
Sponsor:
Gilead Sciences, Inc.
199 E. Blaine Street
Seattle, WA 98102
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
101254
Not Applicable
NTC01090414
Indication:
Hematologic malignancies
Protocol ID:
101-99
Gilead Medical 
Monitor:
Name:
Telephone:
Gilead Clinical 
Program Manager:
Name:
Telephone:
Protocol Version/Date:
Original:
22 January 2010
Amendment 1:
12 April 2010
Amendment 2:
28 October 2013
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the 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 
information is only to be used by you in connection with authorized clinical studies of the 
investigational drug described in the protocol. You will not disclose any of the 
information to others without written authorization from Gilead Sciences, Inc., except to 
the extent necessary to obtain informed consent from those persons to whom the drug 
may be administered.
PPD
PPD
PPD
PPD

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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 .......................................................................................................................................10
Background.....................................................................................................................................10
1.1.
1.1.1.
General Information......................................................................................................10
1.1.2.
Nonclinical Pharmacology and Toxicology..................................................................11
1.1.3.
Clinical Trials of Idelalisib (IDELA)............................................................................11
Rationale for This Study .................................................................................................................14
1.2.
Compliance .....................................................................................................................................15
1.3.
2.
OBJECTIVES..............................................................................................................................................16
3.
STUDY DESIGN ........................................................................................................................................17
Primary Endpoint............................................................................................................................17
3.1.
Secondary Endpoints.......................................................................................................................17
3.2.
Study Design...................................................................................................................................17
3.3.
Study Treatments ............................................................................................................................17
3.4.
Duration of Treatment.....................................................................................................................18
3.5.
Study Discontinuation Criteria........................................................................................................18
3.6.
4.
SUBJECT POPULATION...........................................................................................................................19
Number of Subjects and Subject Selection .....................................................................................19
4.1.
Inclusion Criteria ............................................................................................................................19
4.2.
Exclusion Criteria ...........................................................................................................................19
4.3.
5.
INVESTIGATIONAL MEDICINAL PRODUCT.......................................................................................20
Randomization, Blinding and Treatment Codes .............................................................................20
5.1.
Description and Handling of Idelalisib (IDELA)............................................................................20
5.2.
5.2.1.
Storage and Handling....................................................................................................20
5.2.2.
Formulation...................................................................................................................20
5.2.3.
Packaging and Labeling ................................................................................................20
Dosage and Administration of Idelalisib (IDELA).........................................................................20
5.3.
Dose Adjustment.............................................................................................................................21
5.4.
Study Drug Interruption/Dose Modification...................................................................................21
5.5.
Prior and Concomitant Medications................................................................................................22
5.6.
5.6.1.
Drugs that Alter CYP3A4-Dependent Metabolism.......................................................22
5.6.2.
Drugs that undergo CYP3A-Dependent Metabolism....................................................22
Accountability for Idelalisib (IDELA)............................................................................................23
5.7.
5.7.1.
Idelalisib (IDELA) Return or Disposal .........................................................................23
Treatment Compliance....................................................................................................................23
5.8.
6.
STUDY PROCEDURES .............................................................................................................................24
Subject Enrollment and Treatment Assignment..............................................................................24
6.1.
Study Assessments..........................................................................................................................24
6.2.
Clinical Evaluation..........................................................................................................................25
6.3.
Assessments for Premature Discontinuation from Study................................................................25
6.4.
Criteria for Discontinuation of Study Treatment ............................................................................25
6.5.

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End of Study ...................................................................................................................................26
6.6.
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT........................................................................27
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events..........................27
7.1.
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
Assessment of Adverse Events and Serious Adverse Events..........................................................28
7.2.
7.2.1.
Assessment of Causality for Study Drugs and Procedures............................................28
7.2.2.
Assessment of Severity .................................................................................................29
7.2.3.
Assessment of the Outcome of Adverse Events............................................................29
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
7.3.
Adverse Events to Gilead or CRO ..................................................................................................29
Gilead Reporting Requirements......................................................................................................31
7.4.
7.4.1.
Reporting of Adverse Events Relating to the Primary Endpoint and 
Other Anticipated Medical Events in the Study Population..........................................31
Special Situations Reports ..............................................................................................................32
7.5.
7.5.1.
Definitions of Special Situations...................................................................................32
7.5.2.
Instructions for Reporting Special Situations................................................................32
8.
STATISTICAL CONSIDERATIONS.........................................................................................................34
Determination of Sample Size ........................................................................................................34
8.1.
Statistical and Analytical Plans.......................................................................................................34
8.2.
8.2.1.
General Considerations.................................................................................................34
8.2.2.
Analysis Populations.....................................................................................................34
8.2.3.
Subject Disposition .......................................................................................................34
8.2.4.
Subject Characteristics..................................................................................................34
8.2.5.
Efficacy Analyses..........................................................................................................35
8.2.6.
Pharmacokinetic and Pharmacodynamic Analyses.......................................................35
8.2.7.
Safety Analyses.............................................................................................................35
9.
RESPONSIBILITIES ..................................................................................................................................37
Investigator Responsibilities...........................................................................................................37
9.1.
9.1.1.
Good Clinical Practice ..................................................................................................37
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) Review and Approval..........................................................................................37
9.1.3.
Informed Consent..........................................................................................................38
9.1.4.
Confidentiality ..............................................................................................................38
9.1.5.
Study Files and Retention of Records...........................................................................38
9.1.6.
Case Report Forms........................................................................................................39
9.1.7.
Investigational Medicinal Product Accountability and Return .....................................40
9.1.8.
Inspections ....................................................................................................................40
9.1.9.
Protocol Compliance.....................................................................................................40
Sponsor Responsibilities.................................................................................................................41
9.2.
9.2.1.
Protocol Modifications..................................................................................................41
9.2.2.
Study Report and Publications......................................................................................41
Joint Investigator/Sponsor Responsibilities ....................................................................................41
9.3.
9.3.1.
Access to Information for Monitoring...........................................................................41
9.3.2.
Access to Information for Auditing or Inspections.......................................................42
9.3.3.
Study Discontinuation...................................................................................................42
10.
REFERENCES ............................................................................................................................................43
11.
APPENDICES .............................................................................................................................................45

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Appendix 1.
Investigator Signature Page...........................................................................................46
Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Recommendations...........................................................47
LIST OF IN-TEXT TABLES
Table 5-1.
Dose Modification for Neutropenia and Thrombocytopenia ........................................21
Table 5-2.
Dose Modification for Non-hematologic Toxicity........................................................21
Table 5-3.
Known potent inducers of CYP3A................................................................................22

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
199 East Blaine
Seattle, WA 98102
Study Title: 
An Extension Study to Investigate the Safety and Durability of 
Clinical Activity of idelalisib (IDELA) in Subjects with 
Hematologic Malignacies
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
101254
Not Applicable
NTC01090414
Study Centers 
Planned:
Approximately 19 centers in the United States
Objectives:
The primary objective of this study is as follows:

To investigate the long-term safety of idelalisib (IDELA) in 
patients with hematologic malignancies

To determine the duration of clinical benefit of IDELA in 
patients with hematologic malignancies
Study Design:
This is a long-term safety extension study of IDELA in subjects
with hematologic malignancies who complete other IDELA 
studies. Subjects will be followed according to the standard of care 
as appropriate for their type of cancer, and will be treated at the 
dosage level received upon completion of their prior IDELA study. 
Subjects will be withdrawn from the study if they develop 
progressive disease, unacceptable toxicity related to IDELA, or if 
they no longer derive clinical benefit in the opinion of the 
investigator
Number of Subjects 
Planned:
The number of subjects enrolled will be determined by the number 
of subjects completing a prior IDELA study with a clinical benefit 
and who wish to continue therapy with IDELA
Target Population:
Subjects who complete a prior IDELA study (101-02, 101-07, 
101-08, 101-10) and who are still deriving benefit

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Duration of 
Treatment:
Treatment will continue for as long as the subject derives clinical 
benefit
Diagnosis and Main 
Eligibility Criteria:
Subjects with hematologic malignancies completing  a prior 
IDELA study (101-02, 101-07, 101-08, 101-10)
Study Procedures/
Frequency:
While on study, the subject will return at regular intervals 
(approximately every 2-3 months) for the following procedures: 
evaluation of disease status per standard of care, recording of 
Grade ≥3 AEs and all SAEs, and return of used drug supplies and 
dispensing of new drug supply
While on study, the subject will be followed for disease status 
according to standard of care. At each study visit subjects’ disease 
status will be assessed and information will be collected to 
determine response to treatment. If no change in disease status is 
identified and subject is dispensed additional study drug, the most 
recent prior response documented for the study will be recorded.
All subjects with CLL will have the following laboratory tests at 
each visit: ALC, PLT, Hgb, ANC. All subjects with WM will have 
the following laboratory tests at each visit: IgM, serum M protein
All subjects will have CT scan at least once every 12 months and at 
time of initial response (PR or CR after SD, or CR after PR) or 
progression. In addition, for initial CR a bone marrow evaluation is 
required.
Test Product, Dose, 
and Mode of 
Administration:
IDELA 100, 150 mg, 200 mg BID, or 100 mg, 200 mg, or 300 mg 
QD Oral
Reference Therapy, 
Dose, and Mode of 
Administration:
Not Applicable
Criteria for 
Evaluation:
Subjects who complete a prior IDELA study (101-02, 101-07, 
101-08, 101-10) and who are still deriving benefit
Safety:
Safety will be evaluated by assessing all Grade ≥3 AEs and all 
SAEs.
Efficacy:
Primary Endpoint

Overall response rate (ORR) – defined as the proportion of
subjects who achieve CR,  PR, or MR (for WM only).

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Secondary Endpoints 

Duration of Response (DOR) – defined as the interval from the 
first documentation of CR, PR or MR (for WM) to the earlier 
of the first documentation of definitive disease progression or 
death from any cause

Progression-free survival (PFS) – defined as the interval from
enrollment in the parent study to the earlier of the first 
documentation of definitive disease progression (excluding 
lymphocytosis alone) or death from any cause
Overall survival (OS) – defined as the interval from the start of 
study treatment in the parent study to death from any cause
Pharmacokinetics:
Not Applicable
Statistical Methods:
The intent-to-treat (ITT) analysis set will consist of all subjects
receiving at least 1 dose of study treatment. This analysis set will 
be used for the efficacy and safety analyses.
Subject characteristics and study results will be described and
summarized. Overall response rate based on investigator’s 
response will be calculated along with its 95% confidence intervals
(CIs) based on exact binomial method.
For the analyses of DOR and PFS, the Kaplan-Meier method will 
be used. For data summaries involving continuous variables, data 
tables will typically contain the following information: sample 
size, mean, standard deviation, standard error, median, minimum 
and maximum. For categorical variables, the following information 
will typically be presented: sample size, proportion, and 95% CIs 
based on exact binomial method. Safety will be assessed via grade 
>=3 adverse events (AEs). Summary of efficacy will be presented 
by integrating parent study with 101-99 extension study. All 
treatment emergent adverse events that are observed in the parent 
studies (101-02, 101-07, 101-08, and 101-10) and their extension 
study will be summarized
Sample Size Calculation: Not applicable
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
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
AML
Acute myeloid leukemia
ANC
absolute neutrophil count
AST
aspartate aminotransferase
ATP
Adenosine triphosphate
AUC
area under the concentration-time curve
BID
twice per day
CAL-101
Former name for idelalisib
CFR
Code of Federal Regulations
CI
confidence interval
CLL
chronic lymphocytic leukemia
Cmax
maximum concentration
CR
complete response
CRO
contract research organization
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
Ctrough
trough concentration
Cmax
Maximum concentration
CYP
cytochrome P450 enzyme
DLBCL
diffuse large B-cell lymphoma
DOR
duration of response
DSPH
Gilead Sciences Department of Safety and Public Health
FL
Follicular lymphoma
GCP
Good Clinical Practice
GS-1101
Former name for idelalisib
Hgb
Hemoglobin
IDELA
idelalisib, formerly GS-1101, CAL-101
IMP
Investigational medicinal product
IgM
Immunoglobulin M
iNHL
Indolent non-Hodgkin lymphoma
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ITT
Intent to treat
IWCLL
International Workshop on Chronic Lymphocytic Leukemia
MCL
Mantle cell lymphoma
MTD
Maximum tolerated dose

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
NCCN
National Comprehensive Cancer Network
NOAEL
No observed adverse effect levels
ORR
Overall response rate
OS
Overall survival
PFS
Progression-free survival
PI3K
Phosphatidylinositol 3-kinase
PLT
Platelets
PR
Partial response
QD
Once per day
SAE
Serious adverse event
SD
Stable disease
SLL
Small lymphocytic lymphoma
SOP
Standard Operating Procedure
TTR
Time to Response
WM
Waldenström’s macroglobulinemia

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1.
INTRODUCTION
Background
1.1.
1.1.1.
General Information
Idelalisib (IDELA, GS-1101; formerly CAL-101) is a targeted, highly selective competitive 
inhibitor of the adenosine triphosphate (ATP) binding site of the phosphatidylinositol 
3-kinase (PI3K) p110catalytic domain, which has been shown to be prominently expressed 
in cells of hematopoietic origin {23619}, {17690}. PI3Kδ is critical for multiple signaling 
pathways that are hyperactive in B-cell malignancies. Inhibition of PI3Kδ modulates B-cell 
receptor signaling as well as signaling through cytokine and chemokine receptors and 
integrinl. These signaling pathways act via downstream enzymes (most importantly the 
serine/threonine protein kinase, Akt) to regulate proliferation, apoptosis, motility, homing, 
and retention of malignant B-cells in lymphoid tissues and bone marrow compartments. By 
inhibiting PI3Kδ-dependent signaling, IDELA inhibits proliferation, survival, homing, 
motility, and retention, and promotes apoptosis in many B-cell malignancies.
An essential role of PI3Kδ signaling in the proliferation and survival of hematopoietic cancer 
cells has been demonstrated for several myeloid and B-cell malignancies. Blasts from 
patients with acute myeloid leukemia (AML) have high constitutive PI3K activity, and 
inhibition of PI3Kδ resulted in the inhibition of Akt phosphorylation and cellular 
proliferation {21136}. Sustained activation of the PI3Kδ pathway has been shown to have a 
pivotal role in the survival of B-cell chronic lymphocytic leukemia (CLL) cells co-cultured 
with primary or stromal cell lines {19038}. The Sponsor has shown that PI3Kδ is expressed 
in all primary CLL patient cells tested and treatment with IDELA in vitro led to a decrease in 
viability of most CLL patient cells tested. Constitutive activation of Akt has been 
demonstrated in aggressive blastoid variants of mantle cell lymphoma (MCL) as well as cell 
lines, and treatment of MCL cell lines with the pan-PI3K inhibitor LY294002 resulted in 
apoptosis {21135}. Constitutive activation of AKT has also been reported in diffuse large 
B-cell lymphoma (DLBCL) cell lines and in approximately 50% of DLBCL tissue samples 
{21137}. Treatment with LY294002 resulted in apoptosis of some DLBCL cell lines. The 
PI3K/Akt pathway has also been implicated in survival of follicular lymphoma (FL) cells 
{21134} and Waldenström’s macroglobulinemia (WM) {21146}. These data provide the 
rationale for targeting the PI3Kδ signaling pathway with IDELA as a potential new treatment
for hematologic malignancies. In addition, the relative lack of activity of IDELA against 
p110α should minimize the potential for hyperglycemia relative to pan-PI3K inhibitors.
For further information on IDELA, refer to the current version of the investigator’s brochure 
for IDELA.

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1.1.2.
Nonclinical Pharmacology and Toxicology
A comprehensive set of nonclinical safety and toxicology studies of IDELA have been 
completed and have established no observed adverse effect levels (NOAELs) to support 
clinical studies. Lymphoid depletion in lymphoid tissues was observed in these nonclinical 
studies, which is consistent with the expected pharmacological activity of PI3Kinhibition.
1.1.3.
Clinical Trials of Idelalisib (IDELA)
1.1.3.1.
Phase 1 Monotherapy Study in Patients with Hematological Malignancies 
(Study 101-02)
Study 101-02 was a dose ranging study where IDELA was administered in cohorts of 
subjects across a range of dose levels from 50 mg BID to 350 mg BID. IDELA
administration was continued as long as individual subjects were safely benefitting from 
therapy. Subjects were evaluated in 4-week cycles; response and progression assessments 
were based on standard criteria {12154}.
Study 101-02 has completed enrollment. A total of 191 subjects were enrolled to the study, 
54 of whom had a diagnosis of CLL. In this cohort, the median age was 63 years 
(range 37-82). The disease was considered refractory in 70%, and subjects had a median of 
5 prior regimens. Leukemia cells from 24% of the 54 CLL subjects had del(17p) and/or 
TP53 mutation and 91% had an unmutated immunoglobulin heavy chain variable region 
(IGHV). Pharmacokinetics of IDELA was studied. The multiple-dose Cmax, Ctrough, and 
AUC of IDELA increase in a less than dose proportional manner, with only modest increase 
in exposure observed at the dose level of 350 mg/dose BID (compared with 150 mg). To 
assess the pharmacodynamic effect of IDELA, the phosphorylation status of Akt (a direct 
downstream target of PI3K) in CLL subject samples was investigated. Subject sample 
peripheral blood mononuclear cells (PBMC) were screened for levels of phospho-Akt (pAkt) 
by flow cytometry. At baseline prior to IDELA dosing, a high level of constitutive pAktT308
was noted. Following 8 and 28 days of dosing with IDELA BID, constitutive 
phosphorylation of Akt in cells from subjects with CLL was reduced to the background level 
observed in healthy volunteers. In the evaluation of the effect of IDELA on cytokine 
production, plasma concentrations of CLL-derived chemokines, CCL3 and CCL4, and of the 
stroma-derived chemokine, CXCL13, were elevated at baseline and decreased significantly 
during IDELA administration. IDELA treatment was associated with a peripheral 
lymphocytosis in the CLL subjects, with median ALC approximately doubling over the 
first 8 weeks of treatment, and then descending thereafter. This lymphocytosis is considered 
consistent with inhibition of chemokine signaling, with subsequent redistribution of 
lymphocytes from the lymph node to the blood compartment. 
Study 101-02 was completed prior to a revision in the 2013 National Comprehensive Cancer 
Network (NCCN) guidelines for overall response rate (ORR) that no longer considers 
isolated lymphocytosis as a sign of progressive disease (PD). The revision to the standard 
response criteria was driven by the recent recognition that novel agents (including IDELA) 

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can mobilize CLL cells from tissues into the peripheral blood by interfering with their 
homing and that this represents an expected pharmacologic action rather than an indication of 
disease progression. This effect is especially prominent with monotherapy. These guidelines 
were modified based on a publication by Cheson in 2012 recommending that “persistent 
lymphocytosis should not interfere with the time of designation of a partial response (PR), 
which should be based more on the other measurable aspects of the disease than on 
lymphocytosis” {22541}. Based on data supplied by investigators in the database, and by 
applying the 2013 NCCN and Cheson 2012 criteria, the ORR in CLL subjects was 
72.2% with 22% showing stable disease. {24731}.  Amongst the 13 subjects with 17p 
deletion and/or TP53 mutation, the ORR was 53.8% based on investigator response, and 
amongst the 4 subjects with 17p deletion and/or TP53 mutation who received twice daily 
dosing at ≥150 mg BID, the ORR was 75%. The median Kaplan-Meier estimate of 
progression free survival in all CLL subjects is 17.1 months, and in 28 subjects who received 
twice daily dosing at ≥150 mg per dose, the estimated progression-free survival (PFS) is 
29 months.
Adverse events (AEs) were usually mild to moderate and not clearly IDELA-related. The 
most frequently reported AEs, all grades, in the 54 CLL subjects were fatigue (32%), 
diarrhea (30%), pyrexia (30%), cough (24%), back pain (22%), rash (22%), upper 
respiratatory infection (URI) (22%), and pneumonia (20%). Elevation of alanine 
aminotransferase (ALT) and/or aspartate aminotransferase (AST) was observed in 28%.  
There was no clear dose effect for the occurrence of transaminase elevation.
Although no maximum tolerated dose (MTD) was identified over the dosing range of 
50 to 350 mg BID, the pharmacokinetic, pharmacodynamic and efficacy results led to a 
determination that 150 mg BID would be the recommended phase 2 dose, and this has been 
used in all subsequent studies.
1.1.3.2.
Phase 1 Combination Study in Patients with Hematologic Malignancies 
(Study 101-07)
A separate Phase 1 trial (Study 101-07) has evaluated the safety and preliminary activity of 
IDELA given in combination with bendamustine or bendamustine-rituximab to subjects with 
recurrent iNHL (indolent non-Hodgkin lymphoma) or CLL {20228}, {20229}.
In this study, 28 subjects with CLL received IDELA with bendamustine alone (n=14) or with 
bendamustine/rituximab (n=14). Bendamustine doses were 70 or 90 mg/m2 on Days 1 and 2 
of each of 6 planned 4-week cycles. Rituximab was infused at a dose of 375 mg/m2 on Day 1 
of each of the 6 planned 4-week cycles. IDELA was first evaluated at a dose level of 
100 mg/dose BID (n=4) and then at a dose level of 150 mg/dose BID (n=24) and was 
administered continuously for as long as individual subjects were safely benefiting from 
therapy. Subjects were evaluated in 4-week cycles; response and progression assessments 
were based on standard criteria {12154}.

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Among the subjects with CLL, the median age was 65 and ranged to 86 years. Bulky tumors 
(1 lymph node 5 cm in diameter) were present in 64% of the subjects. The median number 
of prior therapies was 3 and ranged up to 9 prior treatments. The substantial majority (>90%) 
had received prior purine analogs, alkylating agents, and rituximab and 36% had received 
prior bendamustine. Approximately half of subjects had CLL that was refractory to the last 
prior therapy. At the time of data cut-off, therapy had been administered for a median of 
6 cycles, ranging up to 17 cycles (ie, 68 weeks).
No IDELA-related dose-limiting toxicities were observed within the tested subject cohorts. 
Grade 3 neutropenia was observed in 11 (40%) subjects and only 1 (4%) subject had febrile 
neutropenia. Grade 3-4 non-myelosuppressive adverse events largely comprised background 
events resulting from pre-existing disease- or treatment-related conditions or from 
intercurrent illness. Among these subjects with CLL, 4 (15%) developed pneumonia. For 
subjects receiving IDELA together with bendamustine or bendamustine/rituximab, 
Grade 3-4 elevations in ALT/AST were observed in 3 (11%) subjects.
When IDELA was coadministered with bendamustine or bendamustine/rituximab, 
combination therapy showed a high level of antitumor activity. The ITT ORR was 
11/14 (79%) for the IDELA plus bendamustine regimen and 12/14 (86%) among subjects 
receiving IDELA with bendamustine/rituximab. Concomitant administration of 
bendamustine appeared to largely eliminate the redistribution lymphocytosis that is 
associated with IDELA monotherapy. At the time of the data analysis, overall PFS through 
48 weeks was >80% and a median PFS had not yet been observed.
1.1.3.3.
Phase 2 Study of IDELA Plus Rituximab in Treatment Naïve Elderly Patients 
with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma 
(Study 101-08) 
The primary objective of this study was to evaluate the ORR of IDELA when combined with 
rituximab in subjects ≥65 years with previously untreated CLL or small lymphocytic 
lymphoma (SLL).  Enrollment is complete, and 64 subjects have been followed through at 
least 48 weeks. Eligible subjects  received the following treatment regimen:  IDELA 150 mg 
BID orally on Days 1 through 28 of each 28-day cycle (Cycles 1 through 12) + rituximab 
375 mg/m2 IV weekly for 8 doses (Cycles 1 and 2). Treatment with IDELA continued until 
disease progression, unacceptable toxicity, or completion of 12 cycles of therapy. Subjects 
were evaluated by the investigators for response after Cycles 2, 4, 6, 9, and 12 according to 
standard International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria.  
Of the 64 subjects enrolled in the study 62 (96.9%) completed Cycle 2 of the study, and 
43 subjects (67.2%) completed the study (48 weeks).
At baseline, the subjects (N = 64) were predominantly male, white, with median age of 
71 years. The majority of subjects (92.2%) were diagnosed with CLL; 7.8% of subjects were 
diagnosed with SLL.

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The ORR for all subjects (N = 64) for Study 101-08, including subject participation in 
Study 101-99, was 96.9%; 12 subjects (18.8%) had a CR, and 50 subjects (78.1%) had a PR.  
Two subjects (3.1%) were not evaluable, and no subject had a best response of SD or PD on 
study. The ORR for subjects with the del(17p) and/or TP53 mutation or IgHV mutation was 
100% and 95.7%, respectively.  Of note, 3 of 9 subjects with del(17p)/TP53 mutation
achieved CR, and the remainder PR. Among evaluable subjects, the lymph node response 
rate was 98.0%, the splenomegaly response rate was 96.4%, the hepatomegaly response rate 
was 100%, the ALC response rate was 100%, the platelet response rate was 94.1%, the 
hemoglobin response rate was 100%, and the ANC response rate was 100%.The 
Kaplan-Meier estimate of PFS at 24 months was 93%. The median time to response (TTR)
was 1.9 months.
In this study in elderly subjects with previously untreated CLL or SLL, therapy was generally 
well tolerated. The most frequently reported AEs for subjects during either the parent study 
or extension Study 101-99 were diarrhea (55%), pyrexia (42 %), nausea (38%), rash (38%), 
chills (36%), cough (33%), fatigue (31.%), ALT increased (28%), AST increased (27%) and 
pneumonia (27%), dyspnea (23%), headache (23%), vomiting (20%), insomnia (20%),
constipation (17%), pruritus (17%), arthralgia (17%), night sweats (16%), and colitis (16%).  
Eighteen subjects (28.1%) discontinued treatment with IDELA due to one or more AEs. 
Diarrhea, respiratory disorders, and rash were the most frequently reported AEs leading to 
discontinuation of IDELA therapy.  Four subjects (6.3%) died during Study 101-08. The 
causes of death were pneumonitis, pneumonia and metastatic melanoma, drug induced 
pneumonitis and respiratory failure, and sepsis respiratory failure. An additional subject from 
101-08 died during the extension Study 101-99 due to acute myocardial infarction.  
Thirty-seven subjects (48.4%) reported a Serious Adverse Event (SAE) during either the 
parent study or extension Study 101-99. The most commonly reported SAEs were diarrhea 
and pneumonia (10 subjects each, 15.6%) and colitis (7 subjects, 10.9%).
Rationale for This Study
1.2.
This extension study provides the opportunity for subjects with hematologic malignancies 
who have completed a prior study of IDELA to continue IDELA treatment for as long as they 
derive clinical benefit.
Subjects with hematologic malignancies who complete one of the following studies are 
eligible for enrollment:

Study 101-02: A Phase 1 Sequential Dose Escalation Study to Investigate the Safety, 
Pharmacokinetics, Pharmacodynamics, and Clinical Activity of CAL-101 in Patients with 
Select, Relapsed or Refractory Hematologic Malignancies

Study 101-07: A Phase 1 Study to Investigate the Safety and Clinical Activity of 
CAL-101 in Combination with Chemotherapeutic Agents and Anti-CD20 mAb in 
Patients with Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle 
Cell Lymphoma, or Chronic Lymphocytic Leukemia

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
Study 101-08: A Phase 2 Single Arm Study to Investigate the Safety and Clinical 
Activity of CAL-101 in Combination with Rituximab in Elderly Patients with Previously 
Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Study 101-10: Single-Agent GS-1101 (CAL-101) for Previously Treated Low-Grade 
Lymphoma: A Phase 1/2 Study of Safety, Efficacy, and Flow-Cytometric Assessment of 
Tumor-Cell Signaling Events
Compliance
1.3.
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 objectives of this study are:

To investigate the long-term safety of IDELA in subjects with hematologic malignancies

To determine the duration of clinical benefit of IDELA in subjects with hematologic 
malignancies

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3.
STUDY DESIGN
Primary Endpoint
3.1.
The primary endpoint of this study is:

Safety, assessed using Grade ≥3 adverse events according to the Common Terminology 
Criteria for Adverse Events (CTCAE) v4.03
Secondary Endpoints
3.2.
The secondary endpoints of this study are:

Duration of response (DOR) – defined as the interval from the first documentation of CR, 
PR or MR to the earlier of the first documentation of definitive disease progression or 
death from any cause

Progression-free survival (PFS) – defined as the interval from enrollment to the earlier of 
the first documentation of definitive disease progression excluding lymphocytosis alone 
or death from any cause

Overall survival (OS) – defined as the interval from the start of study treatment to death 
from any cause 

Time to response (TTR) – defined as the interval from first dose to the 
first documentation of CR or PR
Study Design
3.3.
This is a long-term safety extension study of IDELA in subjects with hematologic 
malignancies who complete other IDELA studies. Subjects will be followed according to the 
standard of care as appropriate for their type of cancer, and will be treated at the dosage level 
received upon completion of their prior IDELA study. Subjects will be withdrawn from the 
study if they develop progressive disease, unacceptable toxicity related to IDELA, or if they
no longer derive clinical benefit in the opinion of the investigator.
Study Treatments
3.4.
The Sponsor will provide IDELA drug product to study sites. 
Subjects will be treated at the dose level they were receiving at completion of their prior 
IDELA trial.  Subjects receive IDELA in the following doses:

100, 150, or 200 mg IDELA BID

100, 200, or 300 mg IDELA QD

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Subjects receive IDELA in the following formulations:

100-, or 150-mg tablets
Duration of Treatment
3.5.
Treatment will continue for as long as the subject derives clinical benefit. See Protocol 
Section 3.6, Study Discontinuation Criteria, for specific discontinuation criteria
Study Discontinuation Criteria
3.6.
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 study drug treatment for any reason
(see Section 6.5)

The subject experiences a toxicity that necessitates permanent discontinuation of study 
drug treatment

The subject has progressive disease or is no longer deriving clinical benefit

The subject does not comply with the requirements of the protocol

Gilead, a regulatory agency, or an institutional review board (IRB) / independent ethics 
committee (IEC) discontinues the study
The reason for withdrawal will be recorded in the CRF.

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4.
SUBJECT POPULATION
Number of Subjects and Subject Selection
4.1.
A maximum of approximately 250 subjects is anticipated. The number of subjects enrolled 
will be determined by the number of subjects completing a prior IDELA study with a clinical 
benefit who wish to continue therapy with IDELA.
Inclusion Criteria
4.2.
Subjects must meet all of the following inclusion criteria to be eligible for participation in 
this study.

Subjects with hematologic malignancies completing a prior IDELA study 
(101-02, 101-07, 101-08, 101-10) with a clinical benefit are eligible

A negative urine pregnancy test is required for female subjects (unless surgically sterile 
or greater than two years post-menopausal).

Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol specified method(s) of contraception as described 
in Appendix 2.
Exclusion Criteria
4.3.
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

Subjects who are pregnant or nursing will be excluded.

Subjects who are unwilling or unable to comply with the requirements of the protocol 
will be excluded.

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5.
INVESTIGATIONAL MEDICINAL PRODUCT
Randomization, Blinding and Treatment Codes
5.1.
The study is unblinded.
Description and Handling of Idelalisib (IDELA)
5.2.
5.2.1.
Storage and Handling
IDELA, the investigational medicinal product (IMP), will be provided in sealed bottles. The 
bottles should be stored at room temperature (ie, 15-30° C or 59-86° F).  While stability of 
study drug tablets stored at controlled room temperature has been confirmed, brief excursions 
to temperatures as low as 5°C or as high as 40°C (eg, during shipping) will not adversely 
affect the drug. Updated stability data will be provided to the sites, as appropriate.
5.2.2.
Formulation
IDELA drug product is provided as plain-faced, modified oval tablets. The 100-mg tablets 
are orange film-coated, and the 150-mg tablets are pink film-coated.
5.2.3.
Packaging and Labeling
IDELA tablets will be supplied in bottles. A label containing the following information will 
be affixed to the bottle:

Sponsor name and address

Description of contents of package, including dose strength

Caution statement (includes “Keep out of Reach of Children” statement)

Storage conditions

Lot number
The expiry date will be provided in a separate communication and updated as appropriate
Dosage and Administration of Idelalisib (IDELA)
5.3.
IDELA 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 will be treated 
at the dose level they were receiving at completion of their prior IDELA trial.  Subjects 
should be instructed to take the doses with water. IDELA 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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Dose Adjustment
5.4.
The IDELA dose may be increased if the subject has worsening disease but does not meet 
criteria for progressive disease, up to a maximum dose level of 150 mg BID. Dose reduction 
may be considered if severe toxicities occur that may be related to IDELA. 
Recommendations for dose adjustment due to hematologic and non-hematologic toxicity 
follow; 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.
Any planned dose changes should be discussed with the Sponsor prior to implementation.
Study Drug Interruption/Dose Modification
5.5.
Table 5-1.
Dose Modification for Neutropenia and Thrombocytopenia
CTCAE Grade
Drug
Grade 1
(ANC <LLN-
1500/L)
(Plt <LLN-
75,000/L)
Grade 2
(ANC <1500-
1000/L)
(Plt <75,000-
50,000/L)
Grade 3
(ANC <1000-
500/L)
(Plt <50,000-
25,000/L)
Grade 4
(ANC <500/L)
(Plt <25,000/L)
IDELA
Same dose
Same dose
Same dose
Withhold dose for 
toxicity persisting for 
>1 week until 
toxicity grade is 3, 
then resume at same 
dose
Table 5-2.
Dose Modification for Non-hematologic Toxicity
Drug
Grade 1
Grade 2
Grade 3
Grade 4
IDELA
Same dose
Same dose
Withhold dose until 
toxicity grade is 1, 
then reduce by 1 
dose level
Withhold dose until 
toxicity grade is 1, 
then reduce by 1 
dose level
If elevations of serum ALT, AST, or bilirubin are observed, IDELA treatment should be 
withheld and these parameters should be retested within 3 days. If upon retesting, these 
abnormalities are shown to be Grade ≤2, IDELA may be resumed. If the retesting confirms 
Grade ≥3 abnormalities, the sponsor’s medical monitor should be notified. Follow-up 
evaluations on ALT, AST, bilirubin, and alkaline phosphatase should be performed at least 
once per week, until they are stable or resolved.

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Prior and Concomitant Medications
5.6.
Concomitant treatment as deemed medically necessary by the investigator is allowed. No 
other anticancer therapies (including chemotherapy, radiation, antibody therapy, 
immunotherapy, or other experimental therapies) of any kind are permitted while the subject 
is receiving study treatment with IDELA.  Subjects are not allowed to participate 
concurrently in any other therapeutic clinical study.
5.6.1.
Drugs that Alter CYP3A4-Dependent Metabolism
IDELA is metabolized primarily via aldehyde oxidase and in part by CYP3A.  A clinical 
drug-drug interaction study indicated that administration of a potent CYP3A inhibitor 
together with IDELA resulted in an ~80% increase in IDELA plasma exposures (AUC)
{20361}, which is not considered to be clinically relevant and suggests that IDELA is a weak 
CYP3A substrate. Preliminary data indicate that when co-administered with rifampin, a 
highly potent inducer of CYP3A, IDELA exposures are ~75% lower. Co-administration of 
potent inducers of CYP3A with IDELA should be avoided; a list of strong inducers is 
provided in Table 5-3 below:
Table 5-3.
Known potent inducers of CYP3A
Effect on 
CYP3A
Drug Class
Medications
Strong CYP3A 
Inducers
Antimycobacterial
Rifampin
Anticonvulsants
carbamazepine, phenytoin
Foods/herbs
St. John’s wort
Abbreviation: CYP=cytochrome P450 enzyme
5.6.2.
Drugs that undergo CYP3A-Dependent Metabolism
The metabolite of IDELA, GS-563117, is a competitive and time dependent inhibitor of 
CYP3A; accordingly, co-administration of IDELA with midazolam, a probe CYP3A 
substrate, resulted in a ~5-fold increase in midazolam systemic exposure (AUC). 
Co-administration of CYP3A substrates with IDELA may result in an increase in their 
systemic exposures (eg, antiarrhythmics, calcium channel blockers, benzodiazepines, certain 
HMG-CoA reductase inhibitors, phosphodiesterase-5 [PDE5] inhibitors, Warfarin). 
Particular caution is recommended during co-administration of drugs that are highly 
dependent on CYP3A for clearance and for which elevated plasma concentrations are 
associated with serious and/or life-threatening events, including narrow therapeutic index 
CYP3A substrates (eg, alfentanil, cyclosporine, sirolimus, tacrolimus, cisapride, pimozide, 
fentanyl, quinidine, ergotamine, dihydroergotamine, astemizole, terfenadine) with IDELA.

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Accountability for Idelalisib (IDELA)
5.7.
The investigator is responsible for ensuring adequate accountability of all used and unused 
IDELA/supplies. This includes acknowledgement of receipt of each shipment (quantity and 
condition). All unused IDELA, and unused supply, dispensed to subjects must be returned to 
the site.
IDELA accountability records will be provided to each study site to:

Record the date received and quantity of IDELA

Record the date, subject number, subject initials, and lot number, of the IDELA
dispensed.

Record the date, quantity of unused IDELA and used supplies returned, along with the 
initials of the person recording the information.
All study drug records must be maintained at the site and copies must be submitted to 
Gilead Sciences at the end of the study.
5.7.1.
Idelalisib (IDELA) Return or Disposal
The study monitor will evaluate each site’s study drug disposal procedures and provide 
appropriate instruction for return or destruction of unused IDELA supplies. If the site has an 
appropriate Standard Operating Procedure (SOP) for drug destruction, the site may destroy 
unused IDELA and used drug supplies performed in accordance with the site’s 
(hospital/pharmacy) SOPIDELA Where possible, IDELA will be destroyed at the site.  If 
drug is destroyed on site, the Investigator will maintain accurate records for all IDELA
destroyed. See Protocol Section 9.1.7, Investigational Medicinal Product Accountability and 
Return, for additional information.
Treatment Compliance
5.8.
Subject compliance with dosing will be calculated based on return of unused IDELA by 
subjects. The number of tablets dispensed, days of therapy, and number of tablets returned
will be recorded.

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6.
STUDY PROCEDURES
The investigator must document any deviation from protocol procedures and notify the 
Sponsor or Sponsor’s representative.
Subject Enrollment and Treatment Assignment
6.1.
Subjects will sign the informed consent document prior to undergoing any study procedures.
The following information will be collected:

Demographics

Hematologic malignancy diagnosis

Prior IDELA study protocol number

Clinical response status at completion of prior IDELA study

Dose of IDELA at completion of prior IDELA study

Date of Last Subject Visit on prior IDELA study (may be the same date as enrollment to 
this study)

Recording of Grade ≥3 AEs and all SAEs
The subject will be dispensed a supply of IDELA.
Study Assessments
6.2.
From the time of obtaining informed consent through the first administration of 
investigational medicinal product, record all SAEs, as well as any non-serious Grade ≥3 AEs 
on the AE case report form (CRF/eCRF).  All other untoward medical occurrences observed 
during the screening period, including exacerbation or changes in pre-existing conditions are 
considered medical history (not collected for this study).  See section 7 Adverse Events and 
Toxicity Management for additional details.
While on study, the subject will return at regular intervals (approximately every 2-3 months)
for the following procedures:

Evaluation of disease status per standard of care.

Recording of Grade ≥3 AEs and all SAEs

Return of used drug supplies and dispensing of new IDELA supply

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Clinical Evaluation
6.3.
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 and information will be 
collected to determine response to treatment. If no change in disease status is identified and
the subject is dispensed additional IDELA, the most recent prior response documented for the 
study will be recorded.
All subjects with CLL should have the following laboratory test results recorded at each visit: 
ALC, PLT, Hgb, ANC. All subjects with WM should have the following laboratory test 
results recorded at each visit: IgM, serum M protein
All subjects will have CT scan at least once every 12 months and at time of initial response 
(PR or CR after SD, or CR after PR) or progression. In addition, for initial CR a bone 
marrow evaluation is required.
Assessments for Premature Discontinuation from Study
6.4.
If a subject discontinues study dosing (for example, as a result of an AE), every attempt 
should be made to keep the subject in the study and continue to perform the required study-
related follow-up and procedures (see Section 6.5). If this is not possible or acceptable to the 
subject or investigator, the subject may be withdrawn from the study.
Criteria for Discontinuation of Study Treatment
6.5.
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurent illness, the 
subject may resume study dosing at the discretion of the investigator.

Unacceptable toxicity or toxicity that, in the judgment of the investigator, compromises 
the ability to continue study-specific procedures or is considered to not be in the subject’s 
best interest

Subject request to discontinue for any reason

Subject noncompliance
PPD

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
Pregnancy during the study; refer to Appendix 2

Discontinuation of the study at the request of Gilead, a regulatory agency or an IRB/IEC.
End of Study
6.6.
Subjects will be withdrawn from this study if they develop progressive disease, unacceptable 
toxicity related to IDELA, or if they no longer derive clinical benefit in the opinion of the 
investigator. The following procedures should be performed:

Return of used and unused drug supply

Recording of Grade ≥3 AEs and all SAEs

CT scan to document progression

Laboratory assessments

Recording of the reason for withdrawal
Deaths occurring within 30 days following the last dose of IDELA, even if occurring after 
the End of Study Visit, will be captured.

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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
7.1.
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a pharmaceutical 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:

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 (see Section 7.5.1)

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) of 
Grade ≥3 that require medical or surgical intervention or lead to study drug 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 Grade ≥3
or SAE if they meet the definition of an AE or SAE as described in Sections 7.1.1and 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).
Assessment of Adverse Events and Serious Adverse Events
7.2.
The investigator or qualified subinvestigator 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 Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to 
IMP therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. 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 according to CTCAE v4.03. Only AEs ≥ Grade 3 will be 
recorded.
7.2.3.
Assessment of the Outcome of Adverse Events

Resolved: The subject has fully recovered from the event with no residual effects 
observable.

Stabilized: Effects of the event are constant. The likelihood of these effects changing 
(improving or worsening) is low.

Ongoing: Effects of the event are still present and changing. The event is not considered 
stabilized or resolved.
Death is an outcome of an event and not an event per se (sudden death or death of 
unexplainable causes can be reported but follow-up will be required until cause of death is 
determined).
Investigator Requirements and Instructions for Reporting Adverse 
7.3.
Events and Serious Adverse Events to Gilead or CRO
All SAEs, regardless of cause or relationship, which 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 CRF/eCRF database and INC Research Drug Safety 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 4 weeks after last administration of study IMP must be reported to the CRF/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 study IMP, regardless of causality, should also be reported. 

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All Grade ≥ 3 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 IMP, he/she should promptly document and report the 
event to Gilead DSPH.

All Grade ≥ 3 AEs and SAEs will be recorded in the CRF/eCRF database within the 
timelines outlined in the CRF/eCRF completion guideline.

At the time of study start, SAEs will be reported using a paper serious adverse event 
reporting form. During the study conduct, sites may transition to an electronic SAE
(eSAE) system. Gilead will notify sites in writing and provide training and account 
information prior to implementing an eSAE system.
Serious Adverse Event Paper Reporting Process

All SAEs will be recorded on the serious adverse event report form and submitted by 
faxing the report form within 24 hours of the investigator’s knowledge of the event to the 
attention of INC Research Drug Safety.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to INC Research Drug Safety within 24 hours of the investigator’s 
knowledge of the event. Detailed instructions can be found in the eCRF completion 
guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the 
eCRF database is not functioning, record the SAE on the paper serious adverse event 
reporting form and submit within 24 hours as described above.

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been 
locked, no further action is necessary.
INC ResearchDrug Safety:
Fax:
E-mail:
PPD
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
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.
Gilead Reporting Requirements
7.4.
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. The 
investigator should notify the IRB or 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 to the Primary Endpoint and 
Other Anticipated Medical Events in the Study Population
To maintain the integrity of the study, disease progression and death related to disease 
progression should not be reported to Gilead Sciences as adverse events unless it is assessed 
that the study drug caused or contributed to the disease progression or death related to 
disease progression (ie, by a means other than lack of effect). 
All events of disease progression and death related to disease progression, regardless of 
relationship to study drug, will be reported in the eCRFs and, as appropriate, in the final 
clinical study report and in any relevant aggregate safety reports.
Disease progression information from this study will be reviewed on an ongoing basis.

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Special Situations Reports
7.5.
7.5.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, lack 
of effect reports and pregnancy reports regardless of an associated AE.  Also includes reports 
of adverse reactions in infants following exposure from breastfeeding, and reports of adverse 
reactions associated with product complaints and reports arising from occupational exposure.
A pregnancy report is used to report any pregnancy following maternal or paternal exposure 
to the medicinal product.
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 or 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).
Lack of effect is defined as a situation where there is apparent failure of the medicinal 
product or medical technology to bring about the intended beneficial effect on the individual 
in a defined population with a given medical problem, under ideal conditions of use. 
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 all pregnancies that are identified after the subject first 
consents to participate in the study (ie, signs the informed consent) and throughout the study, 
including the post study drug follow-up period, to INC Drug Safety using the pregnancy 
report form within 24 hours of becoming aware of the pregnancy. Refer to section 7.3 and the 
CRF/eCRF completion guidelines for full instructions on the mechanism of pregnancy 
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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 INC Drug Safety.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported INC Drug Safety 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: 
 and Fax: 
Refer to Appendix 2 for Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Recommendations.
7.5.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to INC Drug Safety within 24 hours of the investigator becoming aware of the 
situation. These reports must consist of situations that involve study IMP, but do not apply to 
concomitant medications. Except for situations that result in AEs, special situations involving 
concomitant medications will not be reported. Any inappropriate use of medications 
prohibited by this protocol should not be reported as “misuse,” but may be more 
appropriately documented as a protocol deviation.
Refer to section 7.3 and 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.
PPD
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8.
STATISTICAL CONSIDERATIONS
Determination of Sample Size
8.1.
The sample size for this study depends on the number of eligible subjects from prior studies 
treated with IDELA (101-02, 101-07, 101-08 and 101-10). No formal sample size calculation 
is conducted. 
Statistical and Analytical Plans
8.2.
8.2.1.
General Considerations
The baseline value used in each analysis will be the last value before or on the date of first 
dosing in the parent study. Data from all sites will be pooled for all analyses. Analyses will 
be based upon the observed data unless methods for handling missing data are specified. 
Summary of efficacy will be presented by integrating parent study with this extension study
for 101-02, 101-07, 101-08, and 101-10 respectively
8.2.1.1.
Handling of Missing Data
Analyses will be based upon observed data without imputation.
8.2.2.
Analysis Populations
8.2.2.1.
Intent-to-Treat Analysis Set
The intent-to-treat (ITT) analysis set will consist of all subjects receiving at least 1 dose of 
study treatment. This analysis set will be used for the efficacy and safety analysis. 
The dose of IDELA should be the same as the dose that was administered at the end of the 
parent study.
8.2.3.
Subject Disposition
The number and percentage of subjects who received study drug, completed parent study, 
entered study 101-99 and discontinued from study 101-99 will be summarized. Summary for 
the reasons of the discontinuation from the study treatment will be provided separately for 
each individual study with 101-99.
8.2.4.
Subject Characteristics
Demographics and baseline characteristics information will be captured from parent study. 
Summary will be provided separately for each individual study with 101-99, but will only 
include subjects who rolled over to 101-99. 

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8.2.5.
Efficacy Analyses
Parent studies will be integrated with 101-99 for efficacy analysis. The data will be 
summarized separately for 101-02, 101-07, 101-08 and 101-10 with 101-99 based on subject 
disease and dose categorization as in parent study. The analysis will be performed including
all subjects in the parent study regardless of their rolling over to 101-99 or not.
8.2.5.1.
Primary Efficacy Analysis
Overall response rate based on investigator’s response will be calculated along with its 
95% confidence intervals (CIs) based on exact method. In the analyses of ORR, subjects who 
do not have sufficient baseline or on-study tumor assessment to characterize response will be 
counted in the denominator
8.2.5.2.
Secondary Efficacy Analyses
For the analyses of DOR, PFS and OS, the Kaplan-Meier method will be used. For
categorical variables, the following information will typically be presented: sample size,
proportion, and 95% CIs based on exact binomial method.
For the DOR and PFS analyses, subjects who withdraw from the study or are lost to
follow-up without disease progression or death will be censored on the date of the last visit 
that lack of disease progression was objectively documented. Subjects who start a new 
antitumor treatment other than study treatment before disease progression will be censored 
on the last visit that lack of disease progression was objectively documented before the start 
of new antitumor treatment. Subjects who have CLL progression or die after 2 consecutive 
missing tumor assessments will be censored at the last time prior to the missing assessments 
that lack of definitive CLL progression was objectively documented. For subjects without 
any adequate post-baseline disease assessment, PFS will be censored on the date of 
first study dose.
8.2.6.
Pharmacokinetic and Pharmacodynamic Analyses
Not applicable.
8.2.7.
Safety Analyses
The primary safety endpoint for this study will be the incidence of adverse events. Only 
grade 3 or higher AEs and all serious adverse events (SAEs) encountered by enrolled 
subjects during the clinical trial from the time the informed consent for 101-99 is signed 
through the end of study visit are required to be recorded on the AE CRF page(s). Summary 
will be provided by including all AEs recorded. 

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8.2.7.1.
Extent of Exposure
A subject’s extent of exposure to IDELA will be generated from the IDELA administration 
data. Exposure data will be summarized.
8.2.7.2.
Adverse Events
All adverse events that are observed in the parent studies (101-02, 101-07, 101-08, and 
101-10) and their extension study will be summarized. All Grade ≥3 AEs will be 
summarized. The focus of adverse event summarization will be on treatment-emergent 
adverse events. A treatment-emergent adverse event is defined as an adverse event that 
occurs or worsens in the period from the first dose of study treatment (IDELA or rituximab) 
to 30 days after the last dose of study treatment. Adverse events occurring from the first dose 
administered on the parent study and throughout subjects’ participation in this extension 
study will be included.
Adverse events will be classified using Medical Dictionary for Regulatory Activities 
(MedDRA) with descriptions by System Organ Class (SOC), High-Level Group Term, 
High-Level Term (HLT), Preferred Term, and Lower-Level Term. The severity of adverse 
events will be graded by the investigator according to the CTCAE, Version 4.03, whenever 
possible, and AEs of Grade ≥3 will be recorded. If a CTCAE criterion does not exist for a 
specific type of adverse event, the grade corresponding to the appropriate adjective will be 
used by the investigator to describe the maximum intensity of the adverse event: Grade 3 
(severe), Grade 4 (life threatening), or Grade 5 (fatal). The relationship of the adverse event 
to the study drug will be categorized as related or unrelated.
Summaries (number and percentage of subjects) of treatment-emergent adverse events 
(by SOC, HLT, and preferred term) will be provided.  A subject who reports multiple 
treatment-emergent adverse events within the same preferred term (or HLT or SOC) is 
counted only once for that preferred term (or HLT or SOC) using the worst severity grade. 
Adverse event descriptions will be presented by decreasing frequency for a given SOC, HLT 
and preferred term.
Separate summaries will be prepared for the following types of treatment-emergent adverse 
events:

IDELA-related adverse events

Adverse events that are Grade 3 in severity

Adverse events leading to study drug discontinuation
8.2.7.3.
Serious adverse events.Serious Adverse Events
SAEs will be listed and summarized in a similar manner to AEs as described in 
Section 8.2.7.2.

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9.
RESPONSIBILITIES
Investigator Responsibilities
9.1.
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. For studies conducted in the EU, add: These standards 
are consistent with the European Union Clinical Trials Directive 2001/20/EC and Good 
Clinical Practice Directive 2005/28/EC.
For studies conducted under a United States Investigational New Drug application (IND) 
add:
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 subinvestigators 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 subinvestigator’s) participation in the study. The 
investigator and subinvestigator 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.
Institutional Review Board (IRB)/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 IRB/IEC. The investigator will not begin any study subject 
activities until approval from the IRB/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 IRB/IEC any modifications made to the protocol or any accompanying material to 
be provided to the subject after initial IRB/IEC approval, with the exception of those
necessary to reduce immediate risk to study subjects.

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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 IRB- or IEC-approved consent form for documenting 
written informed consent. Each informed consent (or assent as applicable) will be 
appropriately signed 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 IRB or 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, or IRB.
The investigator agrees that all information received from Gilead, including but not limited to
the investigator brochure, this protocol, CRF/eCRF, the IMP, 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, 
IRB /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);

Documentation that subject meets eligibility criteria, ie, history, physical examination, 
and confirmation of diagnosis (to support inclusion and exclusion criteria);

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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

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 IMP, 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 

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monitoring of safety data.  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 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.
Investigational Medicinal Product Accountability and Return
The study monitor will evaluate each study center’s IMP disposal procedures and provide 
appropriate instruction for destruction of unused IMP supplies. If the site has an appropriate 
standard operating procedure (SOP) for drug destruction as determined by Gilead SOP, the 
site may destroy used (empty or partially empty) and unused IMP supplies in accordance 
with that site’s approved SOP. A copy of the site’s approved SOP will be obtained for central 
files. 
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP
destroyed. Records must show the identification and quantity of each unit destroyed, the 
method of destruction, and the person who disposed of the IMP. Upon study completion, 
copies of the IMP accountability records must be filed at the site. Another copy will be 
returned to Gilead.
The study monitor will review IMP 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 IRBs/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.

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Sponsor Responsibilities
9.2.
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 
IRB in accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.
9.2.2.
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.
Joint Investigator/Sponsor Responsibilities
9.3.
9.3.1.
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.

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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.
9.3.2.
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.
9.3.3.
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), IRBs, 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.
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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-
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de Vos S, Schreeder M, Flinn I, Coutre S, Leonard J, Wagner-Johnston N, et al. A 
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[Abstract #2699]. Blood (ASH Annual Meeting Abstracts) 2011;118.
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Sharman J, de Vos S, Leonard J, Furman R, Coutre S, Flinn I, et al. A phase 1 
study of the selective phosphatidylinositol 3-kinase-delta (PI3Kgamma) inhibitor, 
Cal-101 (GS-1101), in combination with rituximab and/or bendamustine in 
patients with relapsed or refractory chronic lymphocytic leukemuia (CLL) 
[Abstract #1787]. Blood (ASH Annual Meeting Abstracts) 2011;118.
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Webb H, Chen H, Yu A, Peterman S, Holes L, Lannutti B, et al. Clinical 
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Constitutive activation of Akt contributes to the pathogenesis and survival of
mantle cell lymphoma. Blood 2006;108 (5):1668-76.

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

PPD
PPD
ldelalisib (IDELA) 
Protocol 101-99 
Gilead Sciences, Inc. 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
199 E. BLAINE STREET 
SEATTLE, WA 98102 
STUDY ACKNOWLEDGEMENT 
Final 
Version 3.0 
An Extension Study to Investigate the Safety and Durability of Clinical Activity of 
ldelalisib (IDELA) in Subjects with Hematologic Malignancies 
101-99 Protocol Amendment 2, Version 3.0, 28 October 2013 
This protocol has been approved by Gilead Sciences Inc. The follo_w~nature documents 
this approval. 
Date l 
1 
INVESTIGATOR STATEMENT 
I 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. 
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 46 
28 October 2013 

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Appendix 2.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Recommendations
1. Pregnancy and Contraception Requirements for Males and Females of 
Childbearing Potential 
Idelalisib (IDELA) is contraindicated in pregnancy as animal studies in rats and rabbits have 
shown that study drug is teratogenic. Pregnancy must be excluded before the start of 
treatment with study drug and prevented thereafter by reliable contraceptive methods. 
Pregnancy tests will be performed at the start of study treatment, and subjects will be 
required to use contraception throughout the treatment period. Please refer to the latest 
version of the investigator’s brochure for additional information.
2. Definition of Female of Childbearing Potential
For the purposes of this study, a female subject of childbearing potential is a nonmenopausal 
female who has not had a hysterectomy, bilateral oophorectomy, or medically documented 
ovarian failure. This definition includes a pubertal female who has not yet started 
menstruating. A woman who has had a tubal sterilization is considered to be of childbearing 
potential.
A female subject may be considered menopausal in either of the following conditions:

Surgical menopause: Appropriate medical documentation of prior complete bilateral 
oophorectomy (ie, surgical removal of the ovaries and occurring at the age at which the 
procedure was performed)

Spontaneous menopause: Permanent cessation of previously occurring menses as a result 
of ovarian failure with documentation of hormonal deficiency by a certified health care 
provider. The worldwide mean age of spontaneous menopause is 49.24 (SD 1.73) years

A hormonal deficiency should be properly documented in the case of suspected 
spontaneous menopause as follows:

If age 54 years and with the absence of normal menses: serum follicle stimulating 
hormone (FSH) level elevated to within the postmenopausal range based on the 
laboratory reference range where the hormonal assay is performed

If age <54 years and with the absence of normal menses: negative serum or urine human 
chorionic gonadotropin (hCG) with concurrently elevated serum FSH level in the 
postmenopausal range, depressed estradiol (E2) level in the postmenopausal range, and 
absent serum progesterone level, based on the laboratory reference ranges where the 
hormonal assays are performed

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3. Contraceptive Requirements 
Male subjects and female subjects of childbearing potential who engage in intercourse must 
agree to utilize protocol specified methods of contraception from the screening/enrollment 
visit throughout the study period and for 30 days following the last dose of study drug. 
Female study subjects who are not heterosexually active must provide periodic confirmation 
of continued abstinence from heterosexual intercourse and regular pregnancy testing while 
taking IDELA. The investigator will counsel subjects on the protocol specified method(s) for 
avoiding pregnancy in case the subject chooses to engage in heterosexual intercourse.
Protocol specified contraceptive methods are as follows: (1) a combination of one hormonal 
method and one barrier method; (2) two barrier methods where one method is the male 
condom; or (3) use of an intrauterine device (IUD) or tubal sterilization; see 
Appendix Table 1 below. Acceptable hormonal methods include injectable progesterone, 
progesterone implants, combination oral contraceptives, transdermal contraceptive patch, and 
vaginal ring. Acceptable barrier methods include diaphragm with spermicide, cervical cap 
with spermicide, and the male condom. Female subjects must use either a hormonal method 
or a barrier method if the partner has a vasectomy. If a subject has undergone tubal 
sterilization or has had a Copper T 380A IUD or LNg 20 IUD inserted, no other 
contraception is needed.  
If tubal sterilization is via the Essure procedure, verification of tubal blockage by 
hysterosalpingogram (HSP) must be performed approximately 3 months after microinsertion. 
Prior to verification, Essure is not considered a reliable form of contraception and the 
contraception methods described below must be used. Female subjects who utilize hormonal 
contraceptives as one of their birth control methods must have used the same method for at 
least 3 months before study dosing.
Female subjects of childbearing potential must have a negative serum pregnancy test at 
screening and a negative urine pregnancy test at baseline (Day 1) prior to receiving the first 
dose of study drug. Lactating females must discontinue nursing before IMP administration.
Appendix Table 1.
Protocol Specified Contraceptive Methods
Methods to Use by 
Themselves
Combination Methods
Hormone Methods
(choose one and use with a barrier 
method)
Barrier Methods
(use both OR choose one and use 
with a hormone method)
Intrauterine Devices (IUDs)

Copper T 380A IUD

LNg 20 IUD
Tubal Sterilization
Estrogen and Progesterone

Oral contraceptives

Transdermal patch

Vaginal ring
Progesterone

Injection

Implant

Diaphragm with spermicide
OR
Cervical cap with spermicide

Male condom (with or without 
spermicide)
Partner’s vasectomy must be used with a hormone or barrier method.

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The investigator will counsel all subjects on the most effective method(s) for avoiding 
pregnancy during the study.
4. Additional Requirements for Male Subjects
Male subjects must agree to use condoms during heterosexual intercourse and avoid sperm 
donation while enrolled in the study and for at least 30 days after administration of the last 
dose of study medication IDELA.
Use of condoms, with or without spermicide, has been proven to decrease the risk of 
transmission of HIV and other sexually transmitted diseases. The use of spermicide is not 
recommended if the subject or subject’s partner is infected with HIV.
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 study drug dose. Subjects 
who become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug 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.