A Phase 2, Multicenter, Randomized Open-Label Study To Determine the Efficacy of Lenalidomide (Revlimid®) Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma
Phase: PHASE2
Conditions: Mantle Cell Lymphoma, Lymphoma, Mantle-Cell
Sponsor: Celgene

',6&/2685(
5('$&7('35272&2/$0(1'0(17
&&0&/
$3+$6(08/7,&(17(55$1'20,=('23(1/$%(/678'<72
'(7(50,1(7+(()),&$&<2)/(1$/,'20,'(5(9/,0,'9(5686
,19(67,*$725¶6&+2,&(,13$7,(176:,7+5(/$36('255()5$&725<
0$17/(&(///<03+20$
7KHLQIRUPDWLRQFRQWDLQHGLQWKHDWWDFKHGUHSRUWLVWKHSURSHUW\RI&HOJHQHDQGVKRXOGQRWEHVKDUHGRU
XVHGIRUDQ\SXUSRVHRWKHUWKDQWKDWIRUZKLFKLWZDVSURYLGHG

&HOJHQHLVFRPPLWWHGWRSURYLGLQJLQIRUPDWLRQDERXWLWVFOLQLFDOWULDOVWRUHVHDUFKHUVDQGSDWLHQWVZLWKWKH
JRDORIIXUWKHULQJVFLHQFHDQGHQKDQFLQJKHDOWKFDUHZRUOGZLGH/DZVDQGUHJXODWLRQVUHTXLUHKRZHYHU
WKDW&HOJHQHSURWHFWVSDWLHQWSULYDF\7KHFRPSDQ\PD\IXUWKHUKDYHOHJDORUFRQWUDFWXDOREOLJDWLRQVQRW
WRGLVFORVHFRPPHUFLDORUWHFKQLFDOLQIRUPDWLRQSURYLGHGE\RUUHODWHGWRFHUWDLQSDUWQHUFRPSDQLHVRU
YHQGRUV

7KHDWWDFKHGUHSRUWLVSUHVHQWHGLQLWVRULJLQDOIRUPDWEXWFHUWDLQLQIRUPDWLRQKDVEHHQUHGDFWHGLQRUGHU
WRFRPSO\ZLWKWKHDIRUHPHQWLRQHGREOLJDWLRQVRUWRSURWHFW&HOJHQH¶VFRQILGHQWLDOFRPPHUFLDO
LQIRUPDWLRQ7KHUHGDFWLRQVDUHEDVHGRQWKHIROORZLQJSULQFLSOHV

x
5HGDFWHGLQIRUPDWLRQKDVEHHQUHSODFHGE\JUH\VSDFHPDLQWDLQLQJRULJLQDOVSDFLQJDQGSDJLQDWLRQ
x
$Q\LQIRUPDWLRQWKDWPLJKWDOORZWKHLGHQWLILFDWLRQRILQGLYLGXDOVKDVEHHQUHGDFWHGIRU
DQRQ\PL]DWLRQ
x
$WWDFKPHQWVWRWKLVUHSRUWWKDWFRQWDLQFRQILGHQWLDOLQIRUPDWLRQDUHQRWPDGHDYDLODEOH6XFK
DWWDFKPHQWVLQFOXGHWKRVHWKDWFRQWDLQLGHQWLILDEOHSDWLHQWLQIRUPDWLRQVXFKDVVXEMHFWOLVWLQJV
QDUUDWLYHVDQGSURILOHV7KH\DOVRPD\FRQWDLQFRQILGHQWLDOFRPPHUFLDOLQIRUPDWLRQVXFKDV
PHWKRGRORJLHVDQGK\SRWKHVLVJHQHUDWLQJDQGH[SORUDWRU\DQDO\VHV
x
&URVVUHIHUHQFHVWRWKHVHDWWDFKPHQWVVXFKDVOLQNVWRVXEMHFWOLVWLQJVLQ6HFWLRQDUHQRW
UHGDFWHGIURPWKHERG\RIWKHUHSRUW+RZHYHUWKHK\SHUOLQNVLQWKHHOHFWURQLFGRFXPHQWDUHQR
ORQJHUIXQFWLRQDO
x
,QIRUPDWLRQDERXW&HOJHQHYHQGRUVDQGWKHLUVHUYLFHVDUHUHGDFWHGEHFDXVHPDQ\FRQWUDFWVSURKLELW
GLVFORVXUHRIWKDWLQIRUPDWLRQ)XUWKHUODZVDQGUHJXODWLRQVSUHYHQWXVIURPGLVFORVLQJFHUWDLQ
LQIRUPDWLRQDERXWRXUYHQGRUVRUWKHLUVHUYLFHVEHFDXVHLWLVSURWHFWHGE\FRS\ULJKW

,QIRUPDWLRQDERXW&HOJHQH¶VUHGDFWLRQSROLFLHVDQGWKHDYDLODELOLW\RIDGGLWLRQDOGDWDIURPWKLVUHSRUWPD\
EHIRXQGDWKWWSZZZFHOJHQHFRPUHVHDUFKGHYHORSPHQWFOLQLFDOWULDOVFOLQLFDOWULDOVGDWDVKDULQJ


&(/*(1(35235,(7$5<,1)250$7,21
25<
5<
RWEHVKDUHG
RWEHVKDUHG
FKHUVDQGSD
KHUVDQ
JXODWLRQVUH
JXODWLRQVU
DORUFRQWUDF
RUFRQWUDF
WRFHUWDLQS
FHUWDLQS
LQLQIRUPDW
LQLQIRUPDW
&HOJHQH¶VF
&HOJHQH¶V
SULQFLS
SULQFLSOHV
HV
H\VSDFHPD
VSDFHPD
ILFDWLRQRIL
ILFDWLRQRIL
QFRQILGHQWL
QFRQILGHQWL
WDLQLGHQWLILD
LQLGHQWLI
OVRPD\FRQ
OVRPD\FRQ
LVJHQHUDWLQ
LVJHQHUDWL
DWWDFKPHQWV
WWDFKPHQ
RIWKHUHSR
RIWKHUH
W&HOJHQHY
&HOJHQHY
KDWLQIRUPDW
KDWLQIRUPD
DERXWRXUY
DERXWRXU
RQDERXW&H
DERXW&
QGDWKWWSZ
QGDWKWWSZ

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
1
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
TITLE PAGE
A PHASE 2, MULTICENTER, RANDOMIZED OPEN-LABEL 
STUDY TO DETERMINE THE EFFICACY OF LENALIDOMIDE 
(REVLIMID®) VERSUS INVESTIGATOR’S CHOICE IN 
PATIENTS WITH RELAPSED OR REFRACTORY MANTLE 
CELL LYMPHOMA
The “SPRINT” trial
STUDY DRUG:
Lenalidomide
PROTOCOL NUMBER:
CC-5013-MCL-002
DATE
21 October 2008
Amendment # 1
21 April 2009
Amendment # 2
14 December 2009
Amendment # 3
29 April 2011
Amendment # 4
27 September 2011
Amendment # 5
22 March 2013
Amendment # 6
31 May 2018
EudraCT NUMBER
2008-003389-25
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
Printed Name of Celgene Therapeutic Area Head
Date Signed __________________
dd/mmm/yy
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for 
review by you, your staff, and ethics committee/institutional review board.  The information 
contained in this document is regarded as confidential and, except to the extent necessary to 
obtain informed consent, may not be disclosed to another party unless such disclosure is 
required by law or regulations.  Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further disclosed by them.
&(/*(1
otocol is pr
tocol is pr
w by you, y
w by you, y
ntained in t
ntained in
(1(3523
52
d Name of 
d Name o
Da
D
obtain in
obtain in
requ
requ
inf
in
(1
(1
&
235,(7$5<,1)250$7,21
9
mber 2011
ber 2011
rch 2013
rch 201
May
May 2018
201
2008-003
2008-003
tronic signa
ronic sig
5,(
gene Thera
ene Thera
523

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
2
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd/mmm/yy
Printed Name of Site Principal Investigator and Title
Site Number________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
IRB/EC procedures, instructions from Celgene representatives, the Declaration of 
Helsinki, ICH Good Clinical Practices guidelines, and the applicable parts of the United 
States Code of Federal Regulations and local regulations governing the conduct of 
clinical studies.
&(/*(1(35235,(7$5
$5
$5<,1)250$7,21
0$
0$
0$
0$
udy
dy at my
at my
y
s
y
formed cons
rmed c
he Decl
Declarat
ara
licable part
icable pa
overning th
verni
$5

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
3
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
1.
STUDY CONTACT INFORMATION
Table 1:
Celgene Emergency Contact Information
Role in Study
Name
Address and Telephone Number
Responsible Clinical 
Research Physician / 
Medical Monitor
 
86 Morris Avenue 
Summit, NJ 07901
Phone :  
Mobile : 
Lead Study Manager
Celgene R&D SARL
Phone:  
Mobile : 
International Drug Safety 
Contact for EU countries
For Local Drug Safety 
Affiliate Office contact 
information, please refer 
to the Serious Adverse 
Event Report Form 
Completion Guidelines
Clinical Trial Safety
Celgene International Sàrl 
Route de Perreux 1
2017- Boudry –Switzerland
Phone: 
Fax:    
Drug Safety Contact for 
ex-EU countries
Global Drug Safety (North 
America)
Celgene Global Drug Safety
86 Morris Avenue
Summit, NJ 07901
Phone:
 
Fax:    
Email: 
Name of central laboratory(ies) and other medical and/or technical department(s) and /or 
institutions
 
&(/*(1(35235,(7$5<,1)250$7,21
$7
0$
Sàrl
Sàrl
Switzerland
Switzerland
)2
Celgene 
Celgen
86 Mo
86 M
Su
Su
7$
23 ,(
(ies) and ot
ies) and o
5
< ,
5<
$5<
1(3
(1
*(1
/*(
/*
(/*
&(/
&(

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
4
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
2.
SYNOPSIS
Name of Sponsor/Company:  Celgene Corporation
Name of Investigational Product:  Lenalidomide/CC-5013
Protocol Number:  CC-5013-MCL-002
Protocol Title:  A Phase 2, multicenter, Randomized open-Label study to determine the 
efficacy of lenalidomide (revlimid®) versus investigator’s choice in patients with relapsed or 
refractory mantle cell lymphoma
Indication: Relapsed/refractory Mantle Cell Lymphoma (MCL)
Phase of development: Phase 2 Extended Access Phase
Study Duration:
Patients will continue study treatment until disease progression, unacceptable toxicity, or 
voluntary treatment withdrawal. Patients will be followed for survival until either 70% of the 
patients have died, or the median follow-up in responding patients is > 2 years, or the median 
duration of response (overall response and complete response [CR] / complete response 
unconfirmed [CRu]) has been reached, or 4 years from last patient randomized, whichever 
comes later, at which time the study will end for subjects still on lenalidomide treatment in 
countries where lenalidomide is available post-trial in the commercial setting. These subjects 
will have a “discontinuation from treatment” visit at the end of their 7 day rest period from 
their last on-study treatment cycle. At this “discontinuation from treatment” visit commercial 
lenalidomide will be dispensed to the subject. Between this visit and 28 days after, if a patient 
experiences a SAE, this SAE will be reported via the standard post marketing process. A 
pregnancy test should be performed 28 days post treatment discontinuation visit.
An Extended Access Phase will be made available for subjects on study treatment in 
countries where lenalidomide is only available under a clinical trial protocol as post-trial 
access. These subjects will have a “discontinuation from treatment” visit assessment prior to 
being transferred to the Extended Access Phase. 
The Extended Access Phase will end for ongoing subjects still on lenalidomide treatment as 
soon as lenalidomide can be accessed in the commercial setting. 
Guidance on the schedule of assessments for the Extended Access Phase is provided in 
Table 4.
The clinical database will be locked after the last eligible subject has been transferred to post-
trial access in the commercial setting or to the Extended Access Phase, whichever comes 
later. Clinical study data will no longer be collected on CRFs following the clinical database 
lock.
A 28-day safety follow-up assessment will not be required either for subjects transferred to 
post-trial access in the commercial setting or transferred to the Extended Access Phase (after 
the clinical database lock).
For subjects in the Extended Access Phase, SAE forms will be reported to Celgene Safety via 
the standard reporting process for SAEs (including second primary malignancies) in clinical 
trials and, drug accountability information will be reviewed periodically by the study monitor.
&(/*(1(35235,(7$5<,1)250
ble toxicit
ble toxicity
ntil
ntil eiei
l
th
th
i er 7
> 2 years, o
> 2 years,
] / complet
] / complet
ent random
t random
l on lenalid
l on lena
commercia
ommerc
e end of the
e end of t
nuat
nuation fro
f
tween th
tween thisis
via the stan
via the sta
s post treatm
s post treat
e availabl
e available
available u
available u
“discontinu
discontin
ed Access P
d Access 
e will end fo
e will end f
be accesse
e accesse
dule of ass
dule of ass
tabase will 
tabase will
in the comm
n the comm
nical study
cal study
28-day
day saf
saf
y
f
post
post-tri
trialal a
l
th
the clini
clini
or s
50$7,21
$7
$7
$7
$7
0$
50
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
5
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
The End of Trial is defined as either the date of the last visit of the last subject to complete 
the Extended Access Phase or the date of receipt of the last data point from the last subject in 
the Extended Access Phase, whichever comes later.
Objectives:
Primary: 
!
To compare the progression free survival (PFS) of lenalidomide monotherapy 
versus investigator’s choice single agent in patients with mantle cell lymphoma 
(MCL) who are refractory to their regimen or have relapsed once, twice or three 
times.
Secondary:
!
To determine the overall response rate (ORR) of lenalidomide monotherapy or 
investigator’s choice single agent in patients with relapsed or refractory MCL.
!
To evaluate the safety of lenalidomide monotherapy or investigator’s choice single 
agent in patients with relapsed or refractory MCL.
!
To determine the time to progression, and overall survival of patients with 
relapsed or refractory MCL who have received treatment with lenalidomide or 
investigator’s choice single agent.
!
To investigate the health-related quality of life (QoL) of patients treated with 
lenalidomide or investigator’s choice single agent treatment.
 
 
Protocol Amendment #4:
 
 
Study Endpoints:
Primary
!
Progression free survival defined as the time from randomization to the first 
observation of disease progression or death due to any cause. If the patient has not 
progressed or died, PFS will be censored at the time of last completed assessment 
when the patient was known not to have progressed. Patients who will receive a 
new treatment without documented progression will be censored at the last 
assessment date that the patient is known to be progression-free.
&(/*(1(3
Progressio
Progressio
observa
observa
prog
prog
w
&
35235,(7$5<,1)250$7
otherapy or 
otherapy or 
actory
actory MC
MC
y
igator’s ch
igator’s ch
vival o
ival of f pat
pa
tment with
tmen
ife (QoL) o
fe (QoL)
gle agent 
gle agen tr
$7,21
$7
5,(
35,
352
35
( 3

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
6
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Secondary
!
Overall response rate (CR, CRu, and partial response [PR]) assessed by a 
modification of the International Workshop Response Criteria IWRC (Cheson, 
1999).
!
Duration of response
!
Tumor control rate (Rates for CR, CRu, PR, and stable disease [SD])  
!
Time to progression
!
Time to treatment failure
!
Time to tumor response
!
Overall survival (OS)
!
Safety
!
Quality of Life (EORTC QLQ-C30)
Background and Rationale:
Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of lymphoproliferative 
malignancies with differing patterns of behavior and responses to treatment (Armitage, 1993).  
Most (approximately 80-90%) of the NHLs are of B-cell origin and around 10-15% are of T-
cell origin. The prognosis depends on the histologic type, stage, and treatment. Mantle cell 
lymphoma (MCL) is a distinct subtype within B-cell non-Hodgkin’s lymphoma that is 
characterized by the t(11; 14)(q13; q32) chromosomal translocation subsequently leading to 
the overexpression of cyclin D1. This subtype accounts for approximately 5% of all newly 
diagnosed malignant lymphomas.  Although morphologically similar to indolent lymphomas, 
the natural history of MCL is more aggressive than that of indolent lymphomas.  CHOP 
chemotherapy, as well as more intensive chemotherapy regimens such as hyper-CVAD or 
autologous transplantation have been used, often in combination with anti-CD20 monoclonal 
antibody rituximab (Epner, 2007; Pan 2002).  Other agents, such as fludarabine based 
regimens, cytarabine, gemcitabine are also used to treat MCL (Tobinai, 2006).  However, 
MCL remains an incurable disease, and novel therapeutic strategies are needed. The 
increasing understanding of the MCL cell biology has led to the development of new 
therapeutic agents with antitumor activity that target crucial biological pathways, including 
cell cycle inhibitors (i.e. flavopiridol), mTOR inhibitors (i.e. temsirolimus, everolimus), 
proteasome inhibitors (bortezomib) and histone deacetylase inhibitors (Kouroukis, 2003;
Goy, 2005; O’Connor, 2005; Hess 2009). The combination of these new therapeutic 
strategies with existing standard chemotherapy regimens, and better risk stratification of the 
patients may change the management and outcome of MCL patients (Jares, 2008).
Lenalidomide is a member of immunomodulatory agents, IMiDs®, with potent immuno-
stimulatory, anti-angiogenic and pro-apoptotic activities in vitro. It has been shown to have 
efficacy in another B-cell malignancy, multiple myeloma.  Preliminary data is available on 
the activity of lenalidomide in relapsed or refractory MCL patients in two Celgene-sponsored 
clinical trials of lenalidomide in aggressive NHL, study CC-5013-NHL-002 and study CC-
5013-NHL-003.  In study CC-5013-NHL-002 of lenalidomide monotherapy in patients with 
&(/*(1(35235,(7$5<,1)250$7
of lymphop
of lymph
onses to tre
nses to tr
ll origin an
origin 
tytype, stage
pe, stage
y
cell
ell n
l on
on-Ho
Ho
mosomal tra
osomal tr
ype accoun
ype accoun
ugh m
ugh morph
orph
ggressive th
ressive th
ensive chem
nsive che
been used
been used
007
007; Pan 2
Pan
mcicitabine ar
tabine a
i
able diseas
able disea
nding of the
nding of t
s wi
s with
th
i
ant
ant
h
itit
bitors (
bitors (i.i e.
inhibitors 
inhibitors
05; O’Conn
onn
gies
gies wi
with
th
i
e
tients m
ents may 
ay 
Lenalido
Lenalidom
stimula
stimula
ffic
ffi
$7,21
&
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
7
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
relapsed or refractory aggressive NHL (Wiernik, 2008), 15 of 49 patients had MCL. In these 
MCL patients lenalidomide therapy achieved an Overall Response Rate (ORR) of 53%. Three 
patients (20%) had a CR or unconfirmed CR, and 5 patients (33%) had a PR. The median 
duration of response was 13.7 months and median PFS was 5.6 months. The most common 
grade 4 adverse event was thrombocytopenia (13%) and the most common grade 3 adverse 
events were neutropenia (40%), leucopenia (27%), and thrombocytopenia (20%). 
(Habermann, 2009). In another ongoing study of lenalidomide monotherapy in patients with 
relapsed or refractory aggressive NHL (CC-5013-NHL-003), 57 of 217 patients had MCL 
(Witzig, 2011). In the 57 MCL patients who were evaluable for response assessment, 
lenalidomide therapy led to an objective response rate of 42% (25/57). Median progression-
free survival (PFS) was 5.7 months. Overall, the primary side effect of lenalidomide was 
reversible myelosuppression. Grades 3 or 4 neutropenia occurred in 41%, thrombocytopenia 
in 19%, anemia in 9.2%. Grade 3 and grade 4 febrile neutropenia occurred in only 2% of 
patients.
Based on these preliminary observations, the current study is being conducted to evaluate the 
activity and safety of lenalidomide in a larger population of patients with relapsed or 
refractory mantle cell lymphoma.
Study Design:
This is a multicenter, randomized, open-label, comparative controlled phase II study to 
determine the efficacy and safety of single agent lenalidomide over a concurrent control 
group treated with an investigator’s choice single agent in patients with mantle cell 
lymphoma who are refractory to their regimen or have relapsed once, twice or three times
(Figure 1). The study design aims to compare the PFS of lenalidomide therapy over a single 
agent of investigator’s choice. 
The investigator’s choice in the control arm comprises the monotherapy treatment with one of 
the following: chlorambucil, cytarabine, rituximab, fludarabine, or gemcitabine. The 
investigator shall choose the single agent of choice in the control arm for each patient prior to 
randomization on to the study. Patients in the investigator’s choice arm will have the option 
to switch to lenalidomide at time of progressive disease.
Patients will be stratified according to:
!
Time since diagnosis (<3 years or ≥ 3 years)
!
Time since last treatment (<6 months [refractory] or ≥ 6 months)
!
Prior stem cell transplant (yes or no)
Treatment and clinical characteristics will be assessed at screening/baseline, but not used for 
stratification:
!
Number of prior treatment lines (with description of treatment regimens, including 
first line treatment and stem cell transplant)
!
MCL International Prognostic Index (MIPI) score at time of initial diagnosis, if 
available
!
MIPI score at randomization
&(/*(1(35235,(7$5<,
e controlled
controlled
domide ove
mide o
ent in pat
ent in pa iei
have relap
have relap
the PFS of 
he PFS o
arm co
arm comp
m
ine, ri
ine, rituxim
tu
i
le agent of 
agent of 
Pati
Patients in
ents in
time of pro
time of pr
d accordin
d accord
nce diagnos
ce diagno
me since las
me since las
Pri
Prior stem
or stem
ment and cli
ment and cl
tificat
ificatioion:n:
< ,1)250$7,21
on
on-
as
a
cy
cytopeni
topeni
y
a a
ly 2% of
2% of
y
ucted to eva
ucted to eva
ith relapsed
h relaps
$7
!
< ,
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
8
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
!
Ki-67 index in the original pathology specimen at diagnosis, if available or at time 
of relapse
!
Age and gender
!
Absolute lymphocyte counts at baseline
!
Time since last rituximab to cycle 1 day 1
The patients in the study will undergo three consecutive phases:  Screening phase, Treatment 
phase, and Follow-up phase.
Screening phase:
Patients will be screened for protocol eligibility within 28 days prior to randomization as 
outlined in Table 2: Schedule of Study Assessments.  Screening/baseline assessments will 
begin once the patient has accepted and signed the informed consent form. Complete blood 
count (CBC) and serum chemistry tests will be required within 7 days of first dose of study 
drug. Serology, for HBV (at least HBsAg, anti-HBs and anti-HBc) and for HCV will be 
required as screening assessment within 28 days of randomization in endemic areas.
Eligibility for the study is based on the local assessments (CBC, chemistry and serology as 
well as the local results of the archival tumor / lymph node biopsy) done during the 
screening/baseline phase of the study.
Confirmation of mantle cell lymphoma diagnosis by the central pathology is not required 
before randomization or treatment start, but will be performed centrally at a later stage. 
Eligibility for the study is based on assessment of the local pathology results by the 
investigator. Diagnosis based on needle aspirations are not considered acceptable pathologic 
data for entry in this study. 
The confirmation material submitted for Central Pathology Review must include a biopsy-
proven mantle cell lymphoma specimen, including overexpression of cyclin D1 by 
immunohistochemistry. In patients whose tumors are negative for Cyclin D1 overexpression, 
evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable. 
Tumor / lymph node biopsy specimen, which may be archival slides from specimen obtained 
at the time of initial diagnosis, with representative stained slides supporting the diagnosis of 
mantle cell lymphoma (H&E or Giemsa staining and Cyclin D1 staining), must be sent as 
soon as possible to central pathology before randomization but at the latest 8 weeks after 
randomization. It is highly recommended to submit also the original paraffin block (called 
tumor block) which will be returned to the original institution. If the tumor block cannot be 
sent, 4-5 additional unstained slides must be submitted. If such archival tissue is not available 
for submission, then a re-biopsy is required.
The translocation t(11;14)(q13:q32) by FISH is optional and is not sufficient as sole proof for 
diagnosis. Evidence of the translocation t(11;14)(q13:q32) by FISH can be submitted using 
the original slide or the corresponding confirming photographies. If available, it is also 
recommended to send, for central pathology review, slides containing immunostaining for
CD3, CD5, CD10, CD20, CD23, BCL2, Ki-67.
&(/*(1(35235,(7$5<,1)250$7
on as 
as 
ments will
ents will
mplete bl
plete b
m
o
rst dose of 
rst dose o
or HCV w
or HCV w
endemic ar
endemic a
hemistry
hemistry an
psy) done d
psy) done d
central pat
central pat
erform
erformed ce
ed c
the local pa
the local p
ons are not
ons are no
Central Pa
Central Pa
men, includi
n, includi
whose tum
whose tu
yclin D2 o
yclin D2 o
y specimen,
y specimen
nosis, with
nosis, with
a (H&E or 
a (H&E or
 central
entral pat
pa
It i
t is highly
highly
which wil
which wi
ddit
dditioional u
nal u
missio
sion, th
n, th
e transloca
e transloca
didiagnosis.
agnosis.
th
the ori
or g
ecom
ecom
&
$7,21
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
9
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Furthermore, it is highly recommended to perform an unilateral bone marrow biopsy at 
screening, and to send it to Central Pathology for review at the latest 8 weeks after
randomization.
 
During the screening/baseline phase, the investigator must allocate one of the “investigator’s 
choice” options to the patient prior to the randomization.
Treatment phase:
Once all eligibility criteria are met and baseline assessments completed, patients will be 
randomized 2:1 to receive lenalidomide monotherapy or the investigator’s choice. The first 
treatment dose of the first cycle administered to the patient is called C1D1. Treatment should
start as soon as possible after randomization, but maximum time between randomization and 
C1D1 is 4 days, once the patient has fulfilled the requirements of the Lenalidomide
pregnancy prevention program (see Appendix 21.8). Patients will continue in the treatment 
phase until disease progression, unacceptable toxicity or voluntary treatment withdrawal. 
Toxicity will be assessed using the NCI CTCAE criteria version 3 and the dose of 
lenalidomide or the investigators choice single agent will be reduced accordingly (see Table 8
and Table 9 for dose reductions).
Serial assessments of safety and efficacy (CT scans with contrast /MRI with contrast every 56 
days ± 7 days for the first 6 months and then every 90 days ± 15 days thereafter) will be 
performed as outlined in the Schedule of Study Assessments or as directed in the dose 
modification section.  Patients may continue participation in the treatment phase of the study 
until disease progression or unacceptable toxicity or voluntary patient withdrawal from 
treatment, at which point, the patients will enter the follow-up phase.
Diagnostic imaging results (CT scan with contrast/MRI with contrast) will be reviewed 
locally and also sent for central review.
CT scans is the preferred procedure. If CT is contraindicated, MRI is acceptable. It is advised 
to stick to the same procedure for a given patient throughout the study.
 
 
 
 
 
  Patients who withdraw consent for treatment will continue to be followed for 
safety, efficacy (disease progression), second primary malignancies, and for survival.
Prophylaxis for TLS and thromboembolism and assessment and management of tumor 
flare in patients assigned to receive lenalidomide:
Tumor flare and tumor lysis have been reported in patients with chronic lymphocytic 
leukemia treated with lenalidomide. Tumor flare and tumor lysis have also been noted in a 
smaller proportion of patients with non-Hodgkin’s lymphoma treated with lenalidomide, 
&(/*
Pa
P
fet
fety,y, effica
effica
Prophyl
Prophyl
flare
flare
&
(1(3523
wi
35,(7$5<,1)250$7
e
he first 
first 
ment shoul
ent shou
omization 
omizatio
do
domid
m e
ue
ue in the tr
in the tr
atm
atment
ent wi
wi
and the do
nd the do
uced
ce accor
co
contrast
contrast /M
/M
0 days
0 days ± 15
± 15
sessments 
sessments
rtiticipat
cipa ion
icit
icity y or vol
or vo
l enter the f
enter the 
$7,21
th
th
i
contra
contra
h
iew.
ew.
edure. If CT
edure. If CT
ure for a giv
ure for a giv
$7
( 3
1(3
1(
(1
*(
/*(
(/*

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
10
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
based on limited data. Patients in this study should be monitored for tumor flare and tumor 
lysis.
Tumor lysis syndrome
Tumor lysis syndrome (TLS) is a well-known constellation of metabolic abnormalities 
resulting from spontaneous or treatment related tumor necrosis or fulminant apoptosis. The 
metabolic abnormalities include: hyperkalemia, hyperuricemia and hyperphosphatemia with 
secondary hypocalcaemia.
In patients with CLL, the onset of TLS is rapid, usually within 24 to 48 hours after the first 
dose but can also occur after the first week of treatment.  The presence of known risk factors 
like bulky disease, moderate renal insufficiency, high ALC and high uric acid levels (> 8 
mg/dL) prior to therapy increases the likelihood of TLS.  Early identification of patients at 
risk and the prevention of TLS development with the initiation of preventive measures as well 
as the careful monitoring for early signs of laboratory TLS and the prompt initiation of 
supportive care are critical to prevent potentially life-threatening metabolic derangements 
(Cairo, 2004).  
Patients in the lenalidomide arm in this study should receive tumor lysis prophylaxis 
(allopurinol or equivalent) and be well hydrated (orally) during the first 7 days of 
lenalidomide administration in the first cycle or as clinically indicated. Hydration levels 
should be adjusted according to age and clinical status. To monitor for tumor lysis syndrome 
and cytopenia(s), the patients will have a complete blood count (CBC) and chemistry drawn 
on Days 1, 2, 4, 8 and 15 of the first cycle and additionally as clinically indicated. TLS will 
be assessed by Cairo-Bishop Grading system. (See Appendix 21.6).
If a patient develops laboratory TLS (defined by the presence of two or more serum value 
abnormalities of uric acid, potassium, phosphorous or calcium) or ≥ Grade 1 TLS (defined by 
the presence of laboratory TLS and one or more of the following criteria: creatinine ≥ 1.5 x 
ULN, arrhythmia or seizures), appropriate medical management should be initiated according 
to the local standard of care in each institution with vigorous IV hydration (rasburicase 
treatment is considered appropriate if it is approved by the local Health Authority).
Tumor flare reaction 
Tumor flare reaction (TFR) is defined as a sudden and tender increase in the size of the 
disease bearing sites, including the lymph nodes, spleen and or the liver often accompanied 
by low-grade fever, non-pruritic diffuse rash and in some cases increase in the peripheral 
blood lymphocyte counts. In CLL patients, the onset of tumor flare may be as early as within 
a few hours after the first dose and has a median duration of 14 days. This usually occurs 
only during the first cycle of treatment. Tumor flare will be recorded as an AE (graded using 
the NCI CTCAE criteria version 3) and not as progressive disease (PD) and will be treated 
symptomatically first with non-steroidal anti-inflammatory agents (NSAIDs). Narcotics or 
prednisone may be used at the investigator’s discretion, to treat the tumor flare reaction.
Thromboembolism 
All patients treated with lenalidomide regardless of prior thromboembolic history will receive 
prophylactic aspirin [ASA] (70 – 100 mg) daily unless contraindicated.  If ASA is 
&(/*(1(35235,(7$5<,1)250$7
ctors
tors
(> 8 
> 8 
atatieientnts at 
s at 
easures as w
asures as 
nitiat
ia ion of 
n of
ic derangem
c derangem
r lysis prop
r lysis prop
the first 7 d
e first 7
indicated.
indicated
moni
monitor f
tor 
i
od count (C
od count (
ionally
onally as c
a
y
ee Appendi
Appendi
d by
d by the pre
the pre
y
sphorous o
phorous 
e or
or mo
more o
re
opri
opriate med
ate m
ch inst
in ituti
uti
priate if it i
riate if it i
(TFR) is d
(TFR) is
tes, includi
tes, includi
fever, non
ever, non-p
hocy
hocyte cou
te cou
y
urs after th
s after th
during
uring th
the f
e f
NCI
NCI CTCA
CTC
symptom
symptomata
predniso
predniso
hr
&
$7,21
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
11
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
contraindicated, use of low molecular weight heparin or warfarin (or equivalent Vitamin K 
antagonist) to keep the International normalized ratio (INR) in the range of 2-3 may be 
considered.
The choice of prophylactic agent(s), and also the interruption or discontinuation of such 
prophylaxis if needed, should be based on the local standard of care and the investigator’s 
best judgement after careful consideration of the benefit versus the potential risk for the 
individual patient.
Cross over (for patients in the investigators choice Arm B only): 
Patients in the investigator’s choice arm B, who have documented progressive disease will 
have the option to receive single agent lenalidomide treatment. Patients will undergo baseline 
assessments as outlined in the schedule of assessments of Table 3 for Cycle 1 Day 1. 
For patients in Arm B treatment with lenalidomide will start as soon as recovery from 
toxicities of prior treatments. The maximum duration between last day of last cycle of 
treatment in Arm B and first lenalidomide cycle is 10 weeks. Patients in cross-over treatment 
with lenalidomide will be assessed for safety, response evaluation, second primary 
malignancies, and overall survival follow-up. CT scans with contrast /MRI with contrast are 
recommended to be performed every 90 days (± 15 days) from the start of lenalidomide 
cross-over treatment until disease progression or treatment discontinuation for any other 
reason (i.e. toxicity) [Table 3]. Once a patient experiences disease progression or relapse or a 
patient has stopped treatment for other reasons the patient will enter the follow-up phase. In 
the follow-up phase for patients with progressive disease only assessments for safety 
(including second primary malignancies) and overall survival will be done. For patients who 
have entered the follow-up phase due to treatment discontinuation for other reasons 
additionally CT scans with contrast /MRI with contrast will be performed at pre-defined 
intervals and assessments for safety (including second primary malignancies) and overall 
survival will be done. Patients will be followed until either 70% of the patients have died or 
the median follow-up in responding patients is > 2 years or the median duration of response 
(overall response and CR/CRu) has been reached, or four years from last patient randomized, 
whichever comes later, at which time the study will end for ongoing subjects still on 
lenalidomide treatment in countries where lenalidomide is available post-trial in the 
commercial setting. Subjects on study treatment will be transferred to post-trial access in the 
commercial setting (wherever applicable). An Extended Access Phase will be made available 
for subjects on study treatment in countries where lenalidomide is only available under a 
clinical trial protocol as post-trial access. The Extended Access Phase will end for ongoing 
subjects as soon as lenalidomide can be accessed in the commercial setting.
Follow-up phase
Subjects withdrawn for any reason from the Extended Access Phase will not participate in a 
study follow-up phase. At their next visit 28 days later any SAEs experienced during this time 
window will be reported via the standard post-marketing process. Thereafter prescribers will 
be expected to follow the normal post-marketing SAE reporting requirements as applicable in 
their country
&(/*(1(35235,(7$5<,1)250$7
ill
ill
baseline
baseline
1. 
1. 
ry fro
ry from 
m 
st cycle of
st cycle o
cross
cross-over
cond prima
ond prim
st /MRI
/MRI w
he start of 
e start of
sc
scont
ontinuat
inu
 disease pr
disease p
ent will ent
nt will e
sease only
sease only a
y
rall surviva
rall surviva
ment discon
ent disco
itith contras
h contras
luding seco
uding seco
fo
follo
llowed u
wed 
g pat
patieientnts i
s
has been re
has been r
ich t
h time
ime th
t
countries w
countries 
bjects on st
bjects on
wherever a
whereve
udy
udy treatme
treatme
y
otocol as p
otocol as p
oon as lena
on as len
w-up phase
phase
/*
Subjects wit
ubjects wi
&(
study
study f
y ol
ol
f
&
windo
windo
$7,21
&
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
12
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Once a patient experiences disease progression or relapse or a patient has stopped treatment 
for other reasons, the patient will enter the follow up phase.  
!
All patients who discontinue treatment in either study arm or cross-over 
treatment will undergo a safety follow-up visit 28 days after last dosing day for 
assessment of adverse events (including a physical examination), lenalidomide 
counseling and for a medically supervised pregnancy test for FCBP in Arm A and 
in cross over as specified in Appendix 21.8. Vital signs, CBC with differential, 
and serum chemistry are to be performed as clinically indicated. A 28-day safety 
follow-up assessment will not be required either for subjects transferred to post-
trial access in the commercial setting or to the Extended Access Phase. These 
subjects will have a “discontinuation from treatment” visit at the end of their 7 day 
rest period from their last on-study treatment cycle. At this “discontinuation from 
treatment” visit commercial lenalidomide will be dispensed to the subject. 
Between this visit and 28 days after, if a patient experiences a SAE, this SAE will 
be reported via the standard post marketing process. A pregnancy test should be 
performed 28 days post treatment discontinuation visit.
!
Patients who discontinue treatment due to progressive disease or relapse:
∀
Should be followed by clinic visit or documented telephone contact every 90 
days (± 15 days) for survival, second primary malignancies and for the first 
subsequent antilymphoma therapy (including the time of and best response to 
the first antilymphoma treatment regimen utilized after discontinuation from 
treatment in this study)
!
Patients who discontinued treatment due to reasons other than progressive 
disease or relapse:
∀
Clinic visits should occur every 56 days to assess disease status (physical 
exam) until disease progression or relapse
∀
CT scan with contrast/MRI with contrast should occur every 56 days (± 7 
days) until disease progression or relapse up to 6 months from the start of 
study drug then every 90 days ± 15 days thereafter.
∀
After disease progression or relapse has occurred, patients should be followed 
by clinic visit or documented telephone contact every 90 days (± 15 days) for 
survival, second primary malignancies and for the first subsequent 
antilymphoma therapy (including the time of and best response to the first 
antilymphoma treatment regimen utilized after discontinuation from treatment 
in this study).
∀
Patients in the follow-up phase who withdraw consent for efficacy (disease 
progression) follow-up will continue to be followed for second primary 
malignancies and for survival. A full consent withdrawal must be documented 
to disallow survival follow up.
The follow-up phase will continue until either 70% of the patients have died or the median 
follow-up in responding patients is > 2 years or the median duration of response (overall 
&(/*(1(35235,(7$5<,1)250$7
e
heir 7 day
eir 7 day
atatioion n from
from
ubject.
ubject.
AE, this SA
AE, this SA
ancy test sh
ancy test sh
e disease o
e disease 
ted telepho
ted tele
ry m
y
aligna
aligna
uding the tim
ding the 
men utilize
men utilize
nt t due to r
due to r
ur 
ur every 
every 56
5
23
progression
progressi
ntrast
ntrast/MRI
/MR
isease prog
sease prog
g then
hen ever
didisease pro
sease pro
clinic visit
clinic visit
survival
survival, se
s
ant
antilymp
ilym
ant
antily
ily
inin
∀
&
$7,21
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
13
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
response and CR/CRu) has been reached, or four years from last patient randomized, 
whichever comes later, at which time the follow-up study phase will be closed.
Extended Access Phase:
Following the approval of Protocol Amendment #6 an Extended Access Phase will be made 
available for subjects on study treatment in countries where lenalidomide is only available 
under a clinical trial protocol as post-trial access.
These subjects will have a “discontinuation from treatment” visit assessment prior to being 
transferred to the Extended Access Phase.
Following the approval of Protocol Amendment #6, subjects on study treatment will be 
considered to have entered the study Extended Access Phase. Study visits and serial 
measurements of safety should continue to be performed as per guidance outlined in Table 4.
Subjects may remain on study until progressive disease or withdrawal for other reasons. Only 
serious adverse events (SAEs) including second primary malignancies (SPMs), and drug 
accountability record information will be collected and reported for these subjects. Follow-up 
survival data will no longer be collected by Celgene for these subjects.
The Extended Access Phase will end for ongoing subjects still on lenalidomide treatment as 
soon as lenalidomide can be accessed in the commercial setting.
Data Monitoring Committee 
An independent external Data Monitoring Committee (DMC) will review ongoing safety data 
throughout the study and efficacy for futility at a pre-defined time point. Specifics are 
outlined in the DMC charter. The first safety analysis will occur after the first 40 patients 
have received at least 2 cycles of treatment or have discontinued prior to completing 2 cycles.  
The second safety analysis as well as an efficacy analysis for futility will occur after 80
patients complete 2 cycles or withdraw before completing 2 cycles. A third safety analysis 
will occur after 120 patients complete 2 cycles or withdraw before completing 2 cycles. A 
fourth safety analysis will occur after 200 patients complete 2 cycles or withdraw before 
completing 2 cycles.
Independent External Pathological Review
An independent central pathologist will review the lymph node/tumor biopsy for 
retrospective confirmation of the diagnosis of mantle cell lymphoma. 
The confirmation material submitted for Central Pathology Review must include a biopsy-
proven mantle cell lymphoma specimen, including overexpression of cyclin D1 by 
immunohistochemistry. In patients whose tumors are negative for Cyclin D1 overexpression, 
evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable. 
Tumor / lymph node biopsy specimen, which may be archival slides from specimen obtained 
at the time of initial diagnosis, with representative stained slides supporting the diagnosis of 
mantle cell lymphoma (H&E or Giemsa staining and Cyclin D1 staining), must be sent as 
soon as possible to central pathology before randomization, but at the latest 8 weeks after 
randomization. It is highly recommended to submit also the original paraffin block (called 
tumor block) which will be returned to the original institution. If the tumor block cannot be 
&(/*(1(35235,(7$5<,1)250$7
inin Table
Table 4
er reasons
r reasons
PMs), 
PMs), and
and d
se e subjects
subje
ts.
ts.
n lelenalido
idom
ng.
ng.
e (DMC) w
e (DMC) w
pre
pre-defined
defined
nalysis will
nalysis will
or have disc
or have disc
efficacy ana
efficacy an
w before co
before c
etete 2 cy
cycles
c
afafter
ter
f
200 p
0
athologica
thologica
alal patho
pat
lo
rmat
matioion of
n of
ion materia
on materia
ntntle cell lym
le cell lym
histochemi
stochemi
nce of over
nce of over
umor / lym
or / lym
at the tim
at the tim
mant
mantlel
&
$7,21
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
14
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
sent, 4-5 additional unstained slides must be submitted. If such archival tissue is not available 
for submission, then a re-biopsy is required.
The translocation t(11;14)(q13:q32) by FISH is optional and is not sufficient as sole proof for 
diagnosis. Evidence of the translocation t(11;14)(q13:q32) by FISH can be submitted using 
the original slide or the corresponding confirming photographies. If available, it is also 
recommended to send, for central pathology review, slides containing immunostaining for
CD3, CD5, CD10, CD23, CD20, BCL2, Ki-67.
Furthermore, it is highly recommended to perform an unilateral bone marrow biopsy at 
screening, and to send the tumor block to Central Pathology for review at the latest 8 weeks 
after randomization.
 
The central pathologist will also review any pathology specimens obtained as part of response 
assessment, including assessment of bone marrow biopsy required for response assessment of 
CR/CRu.  
For further details, please refer to central pathology manual.
Independent Review Committee (IRC):
The IRC is composed of two external independent radiologists (with an additional radiologist 
adjudicator in the event of a tie) and a hemato/-oncologist. The IRC will perform a blinded, 
independent assessment of radiological response (including assessment of Stable Disease 
[SD] and Progressive Disease [PD]); review the tumor response data and the dates of disease 
progression for each patient. The data reviewed by the IRC will be used in the primary 
analysis and these assessments will be included in the Clinical Study Report. 
∀
Number of patients: approximately 250 randomized patients 
Study Population 
Inclusion Criteria
!
Patients with histologically proven mantle cell non-Hodgkin’s lymphoma [MCL] 
{including overexpression of cyclin D1 by immunohistochemistry}. In patients 
whose tumors are negative for the cyclin D1 overexpression or translocation, 
evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be 
acceptable.
!
Patients who are refractory to their regimen or have relapsed once, twice or three 
times and who have documented progressive disease (Refractory to prior 
chemotherapy regimens is defined as not having reached a CR or PR to prior 
treatment)
!
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 
2
!
Must be #18 years of age at the time of signing the informed consent form.
&(/*(1(35235,(7$5<,1)250
as part of r
as part of
esponse ass
sponse ass
ogists (wi
ogists (with
ti
ogigist. The
st. The I
ncluding as
ncluding 
tumor resp
tumor res
ed by the
ed by the I
luded in the
uded in th
approxima
approx
35
h histol
histol
h
ogi
og
ng 
ng overexp
overex
e tumors ar
e tumors ar
idence of o
dence of
acceptable
acceptable
!
Pati
Patien
en
tim
tim
23
&
50$7,21
ks 
$7
50
2

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
15
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
!
Must have had at least one prior combination chemotherapy regimen with an 
alkylating agent, and comprising either an anthracycline and/or cytarabine and/or
fludarabine (with or without rituximab)
!
Prior stem cell transplant is allowed.
!
Must be ineligible for intensive chemotherapy and/or transplant at time of 
inclusion in the study
!
Must have measurable disease on cross sectional imaging by CT (or MRI, if CT is 
contraindicated) that is at least 2 cm in the longest diameter and measurable in two 
perpendicular dimensions
!
Must be able to adhere to the study visit schedule and other protocol requirements
!
Life expectancy of greater than 3 months
!
Females of childbearing potential (FCBP)† must:
∀
Have two negative medically supervised pregnancy tests prior to starting of 
study therapy. She must agree to ongoing pregnancy testing during the course 
of the study, and after end of study therapy (see specifics in Appendix 21.8).
This applies even if the patient practices complete and continued sexual 
abstinence
∀
Either commit to continued abstinence from heterosexual intercourse (which 
must be reviewed on a monthly basis) or agree to use, and be able to comply 
with, highly effective contraception without interruption, at least 28 days prior 
to starting study drug, during the study therapy (including dose interruptions), 
and for at least 28 days after discontinuation of study therapy (see specifics in 
Appendix 21.8) 
!
Male patients must:
∀
Agree to use a condom during sexual contact with a FCBP, even if they have 
had a vasectomy, throughout study drug therapy, during any dose interruption 
and after cessation of study therapy (see specifics in Appendix 21.8). Agree to 
not donate semen or sperm during study drug therapy and for at least 28 days 
after end of study drug therapy (see specifics in Appendix 21.8 )
!
All patients must:
∀
Have an understanding that the study drug could have a potential teratogenic 
risk.  
∀
Agree to abstain from donating blood while taking study drug therapy and for 
at least 28 days after end of study drug therapy (See specifics in 
Appendix 21.8)
∀
Agree not to share study medication with another person.
∀
Agree to be counseled about pregnancy precautions and risks of fetal 
† Definition found in appendices
&(/*(1(35235,(7$5<,1)250$7
two 
wo 
quirements
uirements
s pri
prior to s
or to
testing dur
esting du
pecifics in
ecifics in
ete and co
ete an
from hetero
from heter
s) or agree 
) or agre
on without 
on withou
he study th
e study th
r didiscont
scontinu
inu
ondom dur
ondom dur
omy, throug
my, throug
essat
ssatioion of
o
ate semen
ate semen
r end of stu
end of stu
patients
patients m
∀
Have a
Have a
ririsk
sk
∀
&
$7,21
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
16
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
exposure.  (See specifics in Appendix 21.8)
Exclusion Criteria
!
Diagnosis of lymphoma other than mantle cell lymphoma
!
Prior history of malignancies, other than mantle cell lymphoma, unless the patient 
has been free of the disease for ≥ 5 years. Exceptions include the following:
∀
Basal cell carcinoma of the skin
∀
Squamous cell carcinoma of the skin
∀
Carcinoma in situ of the cervix
∀
Carcinoma in situ of the breast
∀
Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
!
Transformed lymphoma
!
Prior use of lenalidomide
!
Patients who are candidates for autologous or allogeneic transplantation at the 
time of inclusion in the study
!
Prior allogeneic transplantation with persistent donor hematopoiesis
!
Prior radiotherapy within 4 weeks prior to randomization
!
Active CNS lymphoma with the exception of those patients whose CNS 
lymphoma has been treated with chemotherapy, radiotherapy or surgery, have 
remained asymptomatic for 90 days (3 months) and demonstrate no CNS 
lymphoma as shown by lumbar puncture, CT/brain MRI are eligible.  Patients 
with a history of CNS involvement or CNS symptoms will be required to have 
negative CSF cytology examination and a head CT during the screening period 
(known and active CNS or leptomeningeal involvement). 
!
Known seropositive for or active viral infection with human immunodeficiency 
virus (HIV)
!
Known seropositive for or active viral infection with hepatitis B virus:
∀
HBsAg positive.
∀
HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable
viral DNA.
∀
Patients who are HBsAg negative and viral DNA negative are eligible.
∀
Patients who had hepatitis B but have received an antiviral treatment and show 
no detectable viral DNA for 6 months are eligible.
∀
Patients who are seropositive because of hepatitis B virus vaccine are eligible. 
!
Known seropositive for or active viral infection with hepatitis C virus
∀
Patients who had hepatitis C but have received an antiviral treatment and show 
&(/*(1(35235,(7$5<,1)250$7
of T1a or T
f T1a or 
eic transpla
ic transpl
donor hem
donor he
randomiza
randomiza
ptptioion of tho
n of tho
hemotherap
emothera
day
days (3 m
s (3 mon
on
bar puncture
ar punctur
lvement o
vement o
examinat
xaminatio
CNS or lepto
NS or lep
tive
ive fo
for or 
r or 
seroposit
seropositiv
HBsAg pos
HBsAg pos
HBsAg
HBsAg
viral
viral
∀
$7,21
&
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
17
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
no detectable viral RNA for 6 months are eligible.
!
Patients who are not willing to take DVT prophylaxis, if they are at risk (see 
definition in Section 10.1.6)
!
Patients should not be receiving corticosteroids 7 days prior to randomization,
except for prednisone ≤ 10 mg/day or equivalent for purposes other than treating 
MCL
!
Pregnant or lactating females
!
Any of the additional following laboratory abnormalities:
∀
Absolute neutrophil count (ANC) <1,500 cells/mm3 (1.5 x 109/L)
∀
Platelet count < 60,000/mm3(60 x 109/L)
∀
Serum aspartate transaminase (AST/SGOT) or alanine transaminase 
(ALT/SGPT) > 3.0 x upper limit of normal (ULN), except in patients with 
documented liver involvement by lymphoma
∀
Serum total bilirubin > 1.5 x ULN, except in case of Gilbert’s Syndrome and 
documented liver involvement by lymphoma.
∀
Calculated creatinine clearance (Cockcroft-Gault formula) of < 30 mL/min
!
Any serious medical condition, laboratory abnormality, or psychiatric illness that 
would prevent the patient from signing the informed consent form.
!
Participation in another clinical trial during the screening/baseline phase and 
treatment phase of the study. 
!
Any use of experimental drug during 4 weeks prior to randomization.
Investigational product, dosage and mode of administration [Arm A]: 
!
Patients, who have a creatinine clearance ≥ 60 mL/min, will receive oral 
lenalidomide that is initiated on Day [D] 1 of Cycle 1 at a dose of 25 mg [p.o.] 
once daily for 21 days (D1 – D21) in each 28 day cycle. 
!
Patients who have moderate renal insufficiency [creatinine clearance ≥ 30 mL/min 
but < 60 mL/min] will receive a lower starting dose of lenalidomide of 10 mg 
once daily for 21 days (D1 – D21) in Cycle 1 and Cycle 2.  After Cycle 2, if the 
patient remains free of Grade 3 or Grade 4 toxicity, the dose will be increased to 
15 mg once daily for 21 days (D1 – D21) in each 28 day cycle.
Treatment is to be continued until disease progression or unacceptable toxicity.
Study Drug Supplies: 
Following the approval of Protocol Amendment #6, Celgene Corporation will supply 5 mg, 
10 -mg, 20 mg, and 25 mg strengths in countries where lenalidomide is only available under a 
clinical trial protocol. No more than a 21-day supply of study drug will be dispensed at a 
time.
&(/*(1(3523
and mode 
nd mode
a creatinin
a creatinin
at is init
t is initiate
iate
r 21 day
r 21 days (D
who have m
who have
60 m
60 mL/min
L/min
m
ce daily
ce daily f
y or
f
pati
patient rem
ent rem
15 m
15 mg o
g o
m
tment is to
tment is t
Study Dru
Study Dru
Fo
Follolo
35,(7$5<,1)250$7,21
minase
minase
in pat
in patieientnt
of Gilbert’s
f Gilbert
Gault f
Gault orm
f
bnormalit
normali
he informe
he inform
during the
during the
g during
g during 4
$7
w
0
35
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
18
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Lenalidomide capsules should be swallowed whole, and should not be broken, chewed or 
opened.  Health care providers should consider wearing gloves when directly handling 
Revlimid (lenalidomide) capsules followed by standard hand washing.
Other recommended medications such as aspirin will be provided by the investigative site. 
Celgene will not provide these medications.
Patients in Arm B will receive investigator’s choice single agent reference therapy. This 
includes:
Chlorambucil tablets 2 mg;
Rituximab 500 mg vials;
Cytarabine Injection Solution 100 mg/ml;
Gemcitabine 1g vial;
Fludarabine 10 mg film-coated tablets;
Fludarabine 25mg/ml Concentrate for Solution for Injection or Infusion:
Please refer to the prescribing information provided by Celgene on all of the above
For dosing of the investigators choice single agents, please refer to Table 3 based on 
published data and expert opinions.
Investigators should refer to the approved Summary of Product Characteristics (SPC), 
provided by Celgene, for the investigator’s choice therapy for complete prescribing 
information including administration, warnings, precautions, contraindications, and adverse 
reactions and follow institutional procedures for the administration of the agents, where 
applicable. Paper prints will be provided in the Investigator's and Pharmacy binders.
The investigator’s choice treatment will be provided by Celgene.
Assessments:
Efficacy:
!
Date of documentation of disease progression
!
Overall response rate (PR or better) as defined by a modification of the
International Workshop Response Criteria (Cheson, 1999)
!
Tumor control rate (CR, CRu, PR or SD)
!
CT with contrast/MRI with contrast is performed at baseline then every 56 days
(±7 days) after Day 1, Cycle 1 for the first 6 months and then every 90 days ± 15 
days thereafter until documented progressive disease; or when clinically indicated
To ensure comparability, baseline and on-study methods for response 
assessment must be performed using identical techniques.
!
Bone marrow biopsy if the patient has met all other criteria for CR
cumentatio
cumentatio
ll response 
l response 
rnational
rnational W
Tum
Tumor 
or con
con
!
CT wi
CT w
235,(7$5<,1)250$7,21
fusio
usion:n:
ene
ne on all o
n all o
efer to
efer to Tab
Ta
f Product C
Product 
therapy for
therapy fo
, precaution
precautio
for the adm
for the adm
in the Inves
n the Inve
will be provi
l be prov
$7
(±
(±7
23
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
19
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
!
Physical Exam 
Safety:
!
AEs / SAEs severity is graded using NCI CTCAE criteria version 3.0
!
Vital signs
!
Clinical laboratory evaluations
!
ECOG status 
!
Serum/urine beta-human chorionic gonadotropin (∃-hCG) (FCBP only)
!
Concomitant medications
!
Hospitalizations
!
Second primary malignancies will be monitored as events of interest and must be 
reported as serious adverse events regardless of the treatment arm the subject is in 
(see Section 21.1.9). This includes any second primary malignancy, regardless of 
causal relationship to study drug (lenalidomide or Investigator Choice arm drugs), 
occurring at any time for the duration of the study, from the time of signing the 
Informed Consent Document (ICD) through follow-up for overall survival. The 
Follow-Up Phase involves patient contact every 90 days (± 15 days) until patient 
death or until either 70% of the patients have died, or the median follow-up in 
responding patients is > 2 years, or the median duration of response (overall 
response and CR/CRu) has been reached, or four years from last patient 
randomized, whichever comes later, at which time the follow-up study phase will 
be closed. Events of second primary malignancy are to be reported using the SAE 
report form and must be considered an “Important Medical Event” even if no 
other serious criteria apply; these events must also be documented in the 
appropriate page(s) of the CRF and subject’s source documents.
!
Following the approval of Protocol Amendment #6, only SAE data (including 
SPMs) will continue to be collected and reported to Celgene on SAE CIOMs 
forms for subjects in the Extended Access Phase.
Statistical Analysis:  
Sample Size:
The main objective of the study is to demonstrate the efficacy of lenalidomide over an 
investigator’s choice single agent based on PFS. The primary analysis is to compare PFS 
between lenalidomide and investigator’s choice monotherapy. 
Protocol Amendment #4:
The third independent DMC meeting was held on July 22, 2011, in which the committee 
&(/*(1
l Analysis:
Analysis:
ple Size:
ple Size:
Th
The m
e main o
ain o
investiga
investiga
betwe
betwe
(1
&
1(35235,(7$5<,1)250$7
rest and 
rest and m
arm the sub
rm the sub
ignancy,
nancy, re
igator Cho
gator Cho
m the time
e tim
m
w-up for ov
up fo
y 90 day
90 days (±
(±
didied,
ed, or th
or th
dian durat
dian durat
ed
ed, or r fo
f ur
ur
at which t
at which t
ary
ary m
y
align
align
dered an “I
dered an “I
 these even
these eve
he CRF and
e CRF a
$7,21
oval o
val of Prot
Prot
nue to be c
nue to be c
ects in the 
cts in the
$7
1(
(1(

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
20
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
members reviewed un-blinded both safety and efficacy data from 166 randomized patients. 
No safety concerns were noted.  The DMC observed that the interim PFS in the control arm is 
different from the intial assumptions which were used to calculate the sample size described 
in Protocol Amendment #2.  
The DMC therefore recommended increasing the sample size from 174 (number of patients 
randomized at the time of the DMC was held) to 250 patients and conducting the 
underpowered primary analysis one year after the last patient being randomized. This would 
allow a more reliable estimation of the treatment effect aiming at demonstrating a clinically 
meaningful improvement in PFS between the experimental arm and the control arm. In 
addition, the proposed timing for the analysis will allow a reasonable follow up for overall 
survival so full information on the clinical benefit of lenalidomide can be provided at the time 
of PFS analysis.
The type I error will be controlled with adequate methods and the details will be further 
described in the SAP.
Protocol Amendment #2
With a hazard ratio of 1.7, full information necessary for a one-sided log rank test with an 
overall alpha of 0.025, to have 80% power, will be achieved when approximately 128 patients 
have progressed or died (PFS).
Original Protocol
The sample size of this study was originally calculated to estimate the Overall Response Rate 
(ORR), which was the original objective of the study.  Sample size calculation was based on 
the width of the 95% confidence interval around a certain point estimate for ORR that is 
considered significant clinical activity. Based on preliminary data, a response rate in the 
range of 30% to 40% was reasonably expected.  A sample size equal to 100 allows us to 
construct a two sided 95% confidence interval with a width of 9% (one direction) for an 
expected proportion of 30%. The lower observed confidence interval limit would be about 
21%, which was still considered clinically meaningful. This sample size allowed a width (one 
direction) of 9.6% for an expected proportion of 40% and 9.3% for an expected proportion of 
35% (See Table 10).
Table 9
Confidence Intervals
95% Two-Sided Confidence Intervals (N=100)
Response rate
30%
35%
40%
CI1
0.214 – 0.400
0.257 – 0.452
0.303 – 0.503
1 Exact confidence intervals based on the Clopper-Pearson method
Using a one group χ2 test with a 0.050 two-sided significance level a sample size of 100 
patients will have 81% power to detect the difference between the Null hypothesis proportion 
of 20% and the alternative proportion of 32%. No formal sample size calculation will be done 
for the control arm. With a 2:1 ratio 50 patients are needed in the control arm. Assuming that 
10% of patients will be lost to follow up, 167 patients were to be randomized.
&(/*(1(35235,(7$5<,1)250$7
allll
t the time
the time
l be further
be furthe
ided
de
log r
g r
when appro
when ap
ulated to es
ulated to 
he study. 
study. S
round a cer
round a cer
Based on p
Based on p
y expected.
y expected.
nce interva
ce interv
he l
he lower o
ower o
ered clinica
ered clinic
expected p
xpected p
ence Inter
nce Inter
(1
e rate
rate
*(
/*
(/
Exact confide
xact confide
Using a 
Using a 
pati
patien
en
$7,21
&
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
21
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Efficacy Analysis:
The primary endpoint is progression free survival (PFS). PFS is defined as the time from 
randomization until objective tumor progression or death for any reason. Patients who do not 
progress at the time of analysis will be censored. Progression will be determined according to
the International Workshop Response Criteria (IWRC) (Cheson, 1999), as modified by Fisher 
et al 2006; Kane et al 2007 for target lesions will be used (see Section 21.5 and Table 8 for a 
detailed description of the modifications). The assessment will be reviewed by an 
independent review committee. The primary analysis will be done in the intent-to-treat (ITT) 
population for PFS, overall response rate, overall survival and secondary endpoints. All 
patients who have received at least one single treatment dose (C1D1) with centrally 
confirmed histology of mantle cell non-Hodgkin’s lymphoma will be included in the 
sensitivity analysis. Sensitivity analyses will be conducted for the primary and secondary 
endpoints based on the Full Analysis Set (FAS), and the Per Protocol set (if the PPS 
population differs ≥10% in size from the FAS).
Further secondary endpoints include:
!
Overall response rate (CR, CRu and PR)
!
Duration of response: will be measured from the time of initial response (at least 
PR) until documented tumor progression or death. Patients who do not progress at 
the time of analysis will be censored. This analysis will be restricted to responder
patients.
!
Tumor control rate (Rates for CR, CRu, PR and stable disease [SD])
!
Duration of stable disease: will be calculated as the time from the first evidence of 
stable disease to documented disease progression or documented response or 
death. Patients who do not progress or respond at the time of analysis will be 
censored. This analysis will be restricted to the subgroup of stable disease patients.
!
Time to progression, (TTP) is defined as the time from randomization until 
objective tumor progression; TTP does not include deaths. Patients without 
progression at the time of analysis will be censored. Deaths due to progression of 
disease will be considered as an event.
!
Time to tumor response (TTR) is defined as the time from randomization until 
confirmed response (CR, CRu, PR). Patients with SD or progression at the time of 
analysis will be censored. 
!
TTF is defined as the time from the first dose of study drug to discontinuation of 
treatment for any reason, including disease progression, treatment toxicity or 
death. Patients who are still on drug at the time of the analysis or complete the 
treatment according to the protocol will be censored.
!
Overall survival: defined as the time from randomization until death from any 
cause. Patients alive or lost to follow up at the time of analysis will be censored.
!
QoL (EORTC QLQ-C30)
&(/*(1(35235,(7$5<,1)250$7
) 
e
econdary
condary
he PPS 
e PPS 
me of init
me of 
ia
h. Pati
. Pa ents
nt
nalysis will 
alysis will
u, PR
P
and 
and 
e calculated
calculated
disease prog
sease pro
progress or
progress o
will be restr
will be re
, (TTP) is d
, (TTP) is 
progression
progression
the time of
he time o
be conside
e consi
o tumor res
umor res
firmed resp
firmed resp
nalysis will
alysis wi
TTF is d
TTF is d
treatm
treatm
de
de
&
$7,21
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
22
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
!
Safety
Efficacy analysis will be conducted one year after the last patient is randomized. 
An update of the time to events endpoints and overall survival will be done at the end of the 
follow up. No adjustment for multiplicity will be applied.
All efficacy analysis will be conducted on intent to treat basis.
The Kaplan-Meier procedure will be used to characterize time to event endpoints and 
duration of response. Median times-to-event and their respective two-sided 95% confidence 
intervals will be provided for each of these variables. The stratified log-rank test will be used 
as the main analysis to compare treatment arms for time-to-event variables and an unstratified 
log-rank test will be used as supportive analysis. The Cox proportional hazards regression 
model will be used to assess the significance of stratification factors on treatment differences.
Any demographic or baseline characteristics variables considered as strong predictive or 
prognostic factors will also be included as part of the formal statistical analysis plan. The 
MIPI score at randomization will be analyzed as a stratification factor.
Data will be analyzed and displayed per treatment group in a descriptive manner.
The probability of response rate will be estimated using the proportion of patients with 
responses with exact two-sided 95% confidence intervals.
The EORTC QLQ-C30 will be analyzed using change from baseline and percentage of 
change from baseline according to functional scores and the recommendations in the EORTC 
manual.
The response rate in the cross-over portion of patients in Arm B will be analyzed in a 
descriptive manner.
Interim analysis and DMC:
An independent Data Monitoring Committee will review the safety data and efficacy data for 
futility to assess benefit to risk considerations throughout the study. 
Futility analysis will be conducted when approximately 80 patients complete 2 cycles or 
withdraw before completing 2 cycles (around 54 patients in the lenalidomide arm).
Additional efficacy and safety data might be provided to the DMC members on request as
outlined in the DMC charter.
DMC will conduct an analysis for futility on PFS and Overall response rate. No specific 
stopping rules will be given to the DMC for the PFS; the following rules might be used for 
overall response rate.
&(/*(1(35235,(7$5<,1)250$7
sed d 
ratified 
tified 
essio
ession n
difference
differenc
edictive or 
edictive o
ysis plan
ysis plan. T
ptive mann
tive mann
portion of p
rtion of 
om baselin
baselin
nd 
nd th
the reco
e reco
pat
patieients in A
ts in
n
Committee
mmitte
considerati
considerat
nducted wh
nducted w
eting
ting 2 cycl
c
nd safet
nd saf y d
MC charter
C charter
duct 
duct an 
an ana
an
les will be 
les will be
esponse rat
ponse ra
/*
$7,21
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
23
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Based on a 95% CI approach, if the upper bound is below 20% in the lenalidomide arm, the 
DMC should recommend stopping the trial.
Frequency 
of response
Binomial 
Proportion 
P
Exact Lower
CL, Binomial
Proportion1
Exact Upper
CL, Binomial
Proportion1
1
1.8519
0.04687
9.8915
2
3.7037
0.45173
12.7472
3
5.5556
1.16068
15.3885
4
7.4074
2.05510
17.8933
5
9.2593
3.07528
20.3002
6
11.1111
4.18838
22.6313
7
12.9630
5.37430
24.9012
8
14.8148
6.61976
27.1198
9
16.6667
7.91544
29.2941
10
18.5185
9.25455
31.4297
1Exact confidence intervals based on the Clopper-Pearson method
Safety analysis:
Data from all patients who received at least one dose of study drug will be included in the 
safety analyses.
Adverse event severity will be classified using the NCI CTCAE criteria, version 3.0.
Adverse event frequency will be tabulated by body system, and MedDRA term. 
In the by-patient analysis, a patient having the same event more than once will be counted 
only once. Adverse events will be summarized by worst NCI CTCAE grade. Adverse events 
leading to death or to discontinuation from treatment, events classified as NCI CTCAE grade 
3 or higher, study-drug related events, and serious adverse events will be listed separately.
Second primary malignancies throughout the course of the study will be monitored as events 
of interest, and will be listed and be analyzed separately.
The probability of dose reduction will be estimated using the proportion of patients with dose 
reduction.
Laboratory data will be graded according to NCI CTCAE severity grade.
Extended Access Phase:
For the Extended Access Phase only SAE (including SPMs) data will be reported to Celgene 
drug safety. No statistical analysis is planned to be performed on this safety data. 
&(/*(1(35235,(7$5<,1)250$7
2
41
41
)2
.4297
.4297
1)
,1
on method
n method
study
study drug 
drug 
y
e NCI CTC
e NCI CTC
y body sy
ody systst
ng the same
g the same
mmarized by
marized b
on from tre
from t
vents, and 
vents, and
es througho
es througho
sted and be 
d and be
se reducti
se red
o
ata will be g
ta will be
$7,21
Access Ph
Access Ph
*
he Extended
he Extended
ug safet
ug safety.y. N
&(
$7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
24
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 2:
Schedule of Study Assessments for Arm A and Arm B patients 
(28 days = 1 cycle) 
Procedure
Screening/ Baseline
(-28 Days)
Every Cycle Day 1 ± 3 
days25
Cycle 1
Day 1, 2, 4, 8, 15
Cycles 2-4 Day 15 ± 1
day
Every 56 days After 
Cycle 1 Day 1
± 7 days for the first 6 
months and then every 
90 days ± 15 days 
thereafter
At Treatment 
Discontinuation
Follow-up for patients 
after PD21
Follow-up for non-PD 
patients22
Inclusion/exclusion criteria
X
Complete medical history
X
CNS Lymphoma Evaluation1
X
MCL International Prognostic Index 
(MIPI)2
X
Prior lymphoma therapy
X
Creatinine Clearance (Cockcroft-
Gault estimation)3
X
12-Lead ECG4
X
Lymph node or tumor biopsy 
specimen slides5
X
Eastern Cooperative Oncology Group 
(ECOG) performance status
X
X
X
Vital Signs6
X
X
X
CBC with Differential7
X
X
X9
X
X
Serum Chemistry8
X
X
X9
X
X
Serology HBV, HCV in endemic 
areas
X
Thyroid function test18
X
Pregnancy Testing (FBCP only)
X10
X11
X11
X11
X11
Lenalidomide Counseling and 
distribute lenalidomide Information 
Sheet12
X
X
X13
X13
Assessment of Lymphoma-related 
Symptoms
X
X
X
Adverse Events
X
X
X
X
X
X14
X14
Record Hospitalizations
X
X
Assessment of Second Primary 
Malignancies15
X
X
X
X
X
X
X
Tumor Flare / Tumor lysis 
Assessment16
X16
Concomitant medications/Procedures
X
X
X
X
Physical examination17
X
X
X
X
X
& /*(
pitalization
5235,(7$5<,1)250$7,21
Fo
patie
atie
$7
$7
$7
0$7
0$
0$
50
50
5
25
25
)2
1)2
1)
1)
1)
1)
< ,1
<
$5
7$5
7$5
$5
$5
$5
$5
7$5
(7
(7
(7$
(7$
7$
(7
5,(7
5,(7
X9
(7
(7
(7
(7
(7
5 (7
35
35
X
5,(
5,(
X9
5,(
35
235
235
35
35
235
52
52
X
23
23
23
2
35
352
352
X10
2
52
352
( 35
3
( 3
mat
1(35
35
35
35
35
1(
oma related 
(1(
*(1
(1
*(
(/*
ssment of Sec
&(/
alignancies15
/*
&(
&(
Tumor Flar
&(
essm
&(
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
25
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 2:
Schedule of Study Assessments for Arm A and Arm B patients 
(28 days = 1 cycle) (Continued)
Procedure
Screening/ Baseline
(-28 Days)
Every Cycle Day 1 ± 3 
days25
Cycle 1
Day 1, 2, 4, 8, 15
Cycles 2-4 Day 15
Every 56 days After 
Cycle 1 Day 1
± 7 days for the first 6 
months and then every 
90 days ± 15 days 
thereafter 
At Treatment 
Discontinuation
Follow-up for patients 
after PD21
Follow-up for non-PD 
patients22
CT with contrast (or MRI 
with contrast, if CT 
contraindicated) of neck, 
chest, abdomen and pelvis19
X26
X19
X19
Target and non-target lesion 
measurements19
X
X19
Response assessment
X19
Progression-Free Survival20
X19
X
X
Overall survival
X21
X22
Quality of Life
X23
X23
X23
Bone Marrow Biopsy
X24a
X24b
Dispense study drug25
X25
Study drug return
X
X
1
Patients with a history of CNS involvement or CNS symptoms will be required to have negative CSF cytology 
examination, and a head CT/brain MRI during the screening/baseline period.  
2
MIPI: age, performance status, LDH, absolute leukocyte count, at time of diagnosis, if available.
3
Cockcroft-Gault estimation of creatinine clearance (CrCl): CrCl (mL/min) = (140 – age) (weight [kg]) / 72 
(serum creatinine [mg/dL]); for females, the formula is multiplied by 0.85. Creatinine clearance should be 
determined utilizing actual body weight or ideal body weight, which ever is less (Cockcroft, 1976; Luke, 1990).
4
12-Lead ECG is performed at baseline and as clinically indicated thereafter.
5
Representative slides documenting the diagnosis (H&E or Giemsa staining) and supporting the diagnosis of 
MCL (Cyclin D1 immunostaining), shall be sent together with the tumor block to central pathology as soon as 
possible, preferably before randomization for confirmation of mantle cell lymphoma, but at the latest 8 weeks 
after randomization. In patients whose tumor is negative for Cyclin D1, evidence of overexpression of Cyclin D2 
or D3 is acceptable. Additionally, slides supporting the translocation by FISH or corresponding confirming 
photographies shall be submitted at the same time, if available. It is also recommended to send for central 
pathology review, slides containing immunostaining for CD3, CD5, CD 10, CD23, CD20, BCL2, Ki-67. In case 
the tumor block can not be sent, 4-5 additional, unstained slides must also be submitted. If such archival tissue is 
not available for submission, then a re-biopsy is required.
6
Vital signs include weight, height (only at screening), blood pressure, temperature, and pulse.
7
Complete blood cell count (CBC) will include red blood cell count (RBC), hemoglobin, hematocrit, MCV, white 
blood cell (WBC) count with differential, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), 
and platelet count.
&(/*(1(35235,
5,
5,
t or CNS sym
or CNS sym
during the sc
during the 
, absolute leu
, absolute le
eatinine clea
eatinine cle
or females, th
r females, 
body weight
body we
med at baseli
med at baseli
es documenti
documenti
 immuno
immunostai
stai
erably before
rably befor
mization
mization. In p
In 
acceptable.
ceptable. A
graphies sha
graphies sha
thology revie
thology revi
the tumor bl
he tumor bl
not availa
not availa
Vital
Vital
C
(7$5<,1)250$7,21
F
pati
at
$7
50
50
50$7
0$
X 9
$7
$7
50$7
)25
25
250
50
50
25
25
1)
1)2
1)2
)2
1)2
1)
,1)
1)
1)
1)
1)
1)
1
< ,1
,1
5<,
< ,
$5
$5<
X
b
5<
$
7$
7$
7$5
$5
$5
7$
(7$
7$
7$
7$
7$
7$
(7$
5,(7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
26
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
8
Serum chemistry (total protein, albumin, calcium, phosphorous, glucose, uric acid, total bilirubin, alkaline 
phosphatase, AST, ALT, sodium, potassium, blood urea nitrogen, creatinine and LDH).
9
If screening/baseline assessment hematology, and chemistry labs are performed within 7 days before Cycle 1, 
Day 1, they do not need to be repeated on Cycle 1, Day 1. 
10 Only for patients in Arm A and patients in cross over: before starting study drug: Females of Childbearing 
Potential (FCBP) must confirm that they are using reliable methods of birth control, and must have two negative 
pregnancy tests prior to starting study drug: The first pregnancy test must be performed within 10-14 days prior 
to the start of study drug, and the second pregnancy test must be performed within 24 hours prior to the start of 
study drug. The patient may not receive study drug until the Investigator has verified that the results of these 
pregnancy tests are negative. All patients will be warned that sharing study drug is prohibited and will be 
counseled about pregnancy precautions and potential risks of fetal exposure. (See specifics as described in 
Appendix 21.8).
11 Only for patients in Arm A and patients in cross over: during the study participation and for 28 days following 
discontinuation from the study treatment: FCBP must agree to have two pregnancy tests (See specifics as 
described in Appendix 21.8). In addition to the required pregnancy testing, the investigator must confirm with 
FCBP that she is continuing to use reliable methods of birth control at each visit (See specifics as described in 
Appendix 21.8). 
12 Only for patients in Arm A and patients in cross over: all patients must be counseled about pregnancy 
precautions and risks of fetal exposure.
13 Only for patients in Arm A and patients in cross over: after 28 days post-last dose of lenalidomide.
14 Adverse events will be assessed 28 days post-last dose of treatment during follow-up.
15 Second primary malignancies will be monitored as events of interest and must be reported as serious adverse 
events regardless of the treatment arm the subject is in (see Section 21.1.9). This includes any second primary 
malignancy, regardless of causal relationship to study drug (lenalidomide or Investigator Choice arm drugs), 
occurring at any time for the duration of the study, from the time of signing the ICD through follow-up for 
overall survival. The Follow-Up Phase involves patient contact every 90 days (± 15 days) until patient death or 
until either 70% of the patients have died, or the median follow-up in responding patients is > 2 years, or the
median duration of response (overall response and CR/CRu) has been reached, or four years from last patient 
randomized, whichever comes later, at which time the follow-up study phase will be closed. Events of second 
primary malignancy are to be reported using the SAE report form and must be considered an “Important Medical 
Event” even if no other serious criteria apply; these events must also be documented in the appropriate page(s) of 
the CRF and subject’s source documents. Documentation on the diagnosis of the second primary malignancy 
must be provided at the time of reporting as a serious adverse event (e.g., any confirmatory pathology results, 
imaging results, etc.).
16 Tumor flare / tumor lysis syndrome assessment, only for patients in Arm A, at Cycle 1: Day 2, 4, 8, and 15, and 
when clinically indicated thereafter.
17 Physical examination including lymphadenopathy, hepatomegaly, and splenomegaly as clinically indicated.
Physical examination on study should be done at baseline, Cycle 1 D1 and D15 and then Day 1 of every Cycle. 
18 Thyroid function tests (TSH, fT3, fT4) are performed at baseline/screening only and as clinically indicated.
19 CT with contrast/MRI with contrast must be performed every 56 days (± 7 days) up to 6 months from the start of 
study drug then every 90 ±15 days thereafter, during the follow up phase for patients who have discontinued 
study treatment due to adverse events without evidence of progressive disease. CT scan with contrast /MRI with 
contrast does not need to be performed during follow-up for patients who discontinued due to disease 
progression or relapse. 
20 Progression free survival is assessed until progression of disease or until next lymphoma treatment is given, 
whichever comes first. Patients in the investigators choice Arm B have the option to receive lenalidomide at time 
of documented disease progression.
21 Patients will be followed (clinic visit or documented telephone contact) for overall survival every 90 days (± 15 
days) until death or either 70% of the patients have died or the median follow-up in responding patients is > 2 
years or the median duration of response (overall response and CR/CRu) has been reached, or four years from 
last patient randomized, whichever comes later. At this time the follow-up study phase will be closed. 
&(/*(1(35235,(7$5<,1)250$7,21
following 
following 
cifics as
cifics as
ust confirm w
confirm w
fics
cs as describ
as desc
about pregna
about pregna
ose of lenalid
e of lenalid
follow
ll
-up.p.
d d must be re
must be
1.1.9
1.1.9). This 
). This 
domide or In
domide or In
me of signi
me of signing
ng
tact ever
act every y 90
follow
follow-up in 
up in 
R/CRu) has be
/CRu) has 
he
he follow
follow-up
up
SAE report 
SAE report
these events
these eve
Documentati
Documentati
g as a seriou
as a serio
me assessmen
me assessm
eafter.
after.
uding lympha
ding lym
n study shoul
n study shoul
ts (TSH, fT3
(TSH, fT3
/MRI
/MRI with c
with c
en every 90 ±
very 90 
ment
ment due to a
due to a
does not nee
es not nee
ression or rel
ession or rel
rogression 
rogression f
wh
whichever 
ichever
of docum
docum
Patie
Patie

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
27
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
22 Patients will be followed (clinic visit or documented telephone contact) for overall survival every 56 days (± 7 
days) until death or either 70% of the patients have died or the median follow-up in responding patients is > 2 
years or the median duration of response (overall response and CR/CRu) has been reached, or four years from 
last patient randomized, whichever comes later. At this time the study will end for ongoing subjects still on 
lenalidomide treatment in countries where lenalidomide can be accessed post-trial in the commercial setting. An 
Extended Access Phase will be made available for subjects on study treatment in countries where they can only 
access lenalidomide under a clinical trial protocol as post-trial access. These subjects will have a 
“discontinuation from treatment” visit assessment prior to being transferred to the Extended Access Phase. The 
Extended Access Phase will end for ongoing subjects as soon as lenalidomide can be accessed in the commercial 
setting. Follow-up survival data will no longer be collected by Celgene for these subjects.
23 QoL will be assessed at screening/baseline after Cycle 2 [C3D1] (±7 days), after Cycle 4 [C5D1] (±7 days), after 
Cycle 6 [C7D1] (±7 days), after Cycle 8 [C9D1] (±7 days), and at treatment discontinuation (±7 days).
24a Unilateral bone marrow biopsy is highly recommended at screening that will be submitted to Central Pathology 
for review at the latest within 8 weeks after randomization.
24b Unilateral bone marrow biopsy during treatment is required only if the patient has otherwise fulfilled the criteria 
for CR. The bone marrow procedure should be performed 28 days after the criteria for CR have otherwise been 
met. 
25 Dispense study drug on Day 1 only of each treatment cycle. Cycle 1 should start as soon as possible after 
randomization, but maximum time between randomization and C1D1 is 4 days, once the patient has fulfilled the 
requirements of the Lenalidomide pregnancy prevention program. For lenalidomide, a minimum 7 day rest 
period is mandatory before starting each new treatment cycle regardless of allowed ± visit windows.
 
 
 
 
 
 
 
 
 
 
 
 
27 If a CT scan or MRI was done within 28 days of the randomization, then the CT scan or MRI does not have to be 
repeated for the screening assessment.
&(/*(1(35235,(7$5<,1)250$7,21
after 
af
Pathology 
Pathology 
ulfilled the
filled the c
have otherwi
ave otherw
oon as possib
oon as possib
nce the patien
nce the pati
mide, a minim
mide, a mini
lowed ±
lowed ± visi
vi
5<,
5<
$5<
7$5
7$
(7$
,(7
5,(
35,(
35
235
23
52
352
35
( 35
( 3
1(
(1(
(1
*(1
*(
/*
(/*
&(/
&(
&(
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
28
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 3:
Schedule of study assessments for patients with cross-over on lenalidomide 
after progression in investigator's choice Arm B (28 days = 1 cycle) – No 
more than 10 weeks after last day of last cycle of treatment in Arm B
Procedure
Every Cycle
Day 1 ± 3 days13
Cycle 1
Day 1, 2, 4, 8, 15
Cycles 2- 4
Day 15
Every 90 days After 
Cycle 1 Day 1
± 15 days
At Treatment 
Discontinuation
Follow-up for 
patients after PD11
Follow-up for non-
PD patients12
Eastern Cooperative Oncology Group (ECOG) 
performance status
X
X
Vital Signs1
X
X
CBC with differential2
X
X
X
X
Serum Chemistry3
X
X
X
X
Pregnancy Testing for FCBP4
X
X
Lenalidomide Counseling and distribute 
lenalidomide Information Sheet 5
X
Distribute Lenalidomide counseling sheet5
X
X
Dispense study drug13
X13
Study drug return
X
X
Adverse Events6
X
X
X
X
X6
Assessment of Second Primary Malignancies7
X
X
X
X
X
X
X
Tumor Flare /Tumor Lysis Assessment8
X
Record Hospitalizations
X
X
Concomitant medications/ Procedures
X
X
X
X
CT with contrast (or MRI with contrast, if CT
contraindicated) of neck, chest, abdomen and 
pelvis9
X
X9
Target and non-target lesion measurements
X
Response assessment
X
Progression-Free Survival10
X
X
X
Overall survival
X11
X12
1
Vital signs include weight, blood pressure, temperature, and pulse.
2
Complete blood cell count (CBC) will include red blood cell count (RBC), hemoglobin, hematocrit, MCV, white 
blood cell WBC) count with differential, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), 
and platelet count.
3
Serum chemistry (total protein, albumin, calcium, phosphorous, glucose, uric acid, total bilirubin, alkaline 
phosphatase, AST (SGOT), ALT (SGPT), sodium, potassium, blood urea nitrogen, creatinine and lactate 
dehydrogenase).
&(/*(1(35235,(7$5<,1)250$7,21
Follo
Follo
PD pati
PD pati
0$7,
0$
0$
0$
50
2 0
25
)2
)2
X
)2
)2
)2
)2
)2
X
1)
,1
,1
,1
,1
,1
<
5<
$5
$5
$5
$5
$5
X
7$
(7
X
X
X
(7
(7
(7
(7
X
5,(
3
(
35 (
X
35
35
35
35
X
23
23
T
and 
nd 
2
52
urements
urements
3
(
al10
10
1(
(1
*(
signs include
signs include
omplete bloo
omplete bloo
blood cell
lood cell W
and plate
and plate
Serum
Serum
ph

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
29
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
4
During the study participation and for 28 days following discontinuation from the study treatment: FCBP must 
agree to have pregnancy tests (See specifics as described in Appendix 21.8). In addition to the required 
pregnancy testing, the investigator must confirm with FCBP that she is continuing to use reliable methods of 
birth control at each visit (See specifics as described in Appendix 21.8).
5
All patients must be counseled about pregnancy precautions and risks of fetal exposure.
6
Adverse events will be assessed 30 days post-last dose during follow-up.
7
Second primary malignancies will be monitored as events of interest and must be reported as serious adverse 
events regardless of the treatment arm the subject is in (see Section 21.1.9).  This includes any second primary 
malignancy, regardless of causal relationship to study drug (lenalidomide or Investigator Choice arm drugs), 
occurring at any time for the duration of the study, from the time of signing the ICD through follow-up for 
overall survival. The Follow-Up Phase involves patient contact every 90 days (± 15 days) until patient death or 
until either 70% of the patients have died, or the median follow-up in responding patients is > 2 years, or the 
median duration of response (overall response and CR/CRu) has been reached, or four years from last patient 
randomized, whichever comes later, at which time the follow-up study phase will be closed. Events of second 
primary malignancy are to be reported using the SAE report form and must be considered an “Important Medical 
Event” even if no other serious criteria apply; these events must also be documented in the appropriate page(s) of 
the CRF and subject’s source documents. Documentation on the diagnosis of the second primary malignancy 
must be provided at the time of reporting as a serious adverse event (e.g., any confirmatory pathology results, 
imaging results, etc.).
8
Tumor flare/Tumor lysis assessment at Cycle 1: Day 2, 4, 8, and 15, and when clinically indicated.
9
CT with contrast/ or MRI with contrast must be performed every 90 days (± 15 days) from the start of 
lenalidomide cross-over treatment, and during the follow up phase for patients who have discontinued treatment 
due to adverse events without evidence of progressive disease. CT scan with contrast /MRI with contrast does 
not need to be performed during follow-up for patients who discontinued due to disease progression or relapse. 
10 Progression Free Survival is assessed until progression of disease or until next lymphoma treatment is given, 
whichever comes first.
11 Patients will be followed (clinic visit or documented telephone contact) for overall survival every 90 days (± 15 
days) until death or either 70% of the patients have died or the median follow-up in responding patients is > 2 
years or the median duration of response (overall response and CR/CRu) has been reached, or four years from 
last patient randomized, whichever comes later. At this time the follow-up study phase will be closed. 
12 Patients will be followed (clinic visit and CT scan/MRI) for overall survival every 90 days (± 15 days) from the 
start of lenalidomide cross-over treatment until death or either 70% of the patients have died or the median 
follow-up in responding patients is > 2 years or the median duration of response (overall response and CR/CRu) 
has been reached, or four years from last patient randomized, whichever comes later. At this time the study will 
end for ongoing subjects still on lenalidomide treatment in countries where lenalidomide can be accessed post-
trial in the commercial setting. An Extended Access Phase will be made available for subjects on study treatment 
in countries where they can only access lenalidomide under a clinical trial protocol as post-trial access. These 
subjects will have a “discontinuation from treatment” visit assessment prior to being transferred to the Extended 
Access Phase. The Extended Access Phase will end for ongoing subjects as soon as lenalidomide can be accessed 
in the commercial setting. Follow-up survival data will no longer be collected by Celgene for these subjects.
13 Starting cross-over lenalidomide treatment after disease progression is extensively documented in Arm B should 
be as soon as toxicities of prior Arm B treatments have resolved and all inclusion/exclusion criteria are met, but 
not later than 10 weeks after last day of last Arm B treatment cycle and as soon as the patient has fulfilled the 
requirements of the Lenalidomide pregnancy prevention program. Once lenalidomide treatment is started, a 
minimum 7-day rest period is mandatory before starting each new treatment cycle regardless of allowed ± visit 
windows.
&(/*(1(35
35235,(7$5<,1)250$7,21
ath or 
h or 
or the
the
st patient 
t patient 
ts of second 
ts of second
Important M
mportant M
appropriate p
ppropriate
primary mal
primary m
atory patholo
tory patholo
clinically ind
linically in
15 days
15 days) fro
fro
tients who h
ients w
n with contra
with cont
tinued due to
nued due t
se or until ne
se or until n
phone contac
phone cont
ed or the med
d or the m
es
esponse and C
ponse and C
At this ti
At this time
me
 scan
scan/MRI
/MRI) f
until death o
until dea
years or the 
ears or the
m last patient 
m last patient
lenalidomide
enalidomid
An Extende
An Exten
only access 
only acc
continuation 
continuation
xtended Acce
tended Acc
setting.
etting. Follo
Follo
ver lenalido
ver lenal
toxicities o
toxicities o
han 10 week
an 10 week
ements of the
nts of th
imum 7
mum -day 
day
windows.
indows.

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
30
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 4:
Schedule of Study Assessments: Guidance for Extended Access Phase
Assessment
Day 1 of Each Cyclea
Extended Access Phase
(± 3 days)
Extended Access Phase 
Discontinuation
(at day of 
discontinuation)
Informed consentb
X
Prior to first cycle 
treatment
-
Lenalidomide counseling/distribute lenalidomide 
counseling sheet
X
X
Concomitant medication/therapies
X
recorded in the subjects’
records only
X
recorded in the subjects’
records only
Adverse events including assessment of second 
primary malignanciesc
SAEs only
SAEs only
Study drug dispensation/return/accountability
X
X
CBC with differentiald
X 
As per local practice
X
As per local practice
Serum Chemistrye
X
As per local practice
X
As per local practice
All other safety labs
X
As per local practice
X
As per local practice
Pregnancy Testing (FBCP only)f
X
X
and at 28 days post 
discontinuation treatment 
visit 
ALT = alanine transaminase; AST = aspartate transaminase; FCBP = female of childbearing potential; SGOT = 
serum glutamic-oxaloacetic transaminase; SGPT= serum glutamic-pyruvic transaminase. 
a. A cycle is equal to 28 days.  If the administration of study drug has not been interrupted, the next cycle of therapy 
and assessments are to be given/done as in the Treatment Phase of the protocol.
b. Informed consent for the Extended Access Phase must be signed and dated by subjects in countries where they can 
only continue receiving lenalidomide under a clinical trial protocol.
c. Second primary malignancies (SPMs) will be monitored as events of interest and must be reported as serious 
adverse events.  This includes any SPM, regardless of causal relationship to study drug, occurring at any time for 
the duration of the study, from the time of signing the informed consent up to and including the Extended Access 
Phase. Events of second primary malignancy are to be reported using the SAE report form and must be considered 
an “Important Medical Event” even if no other serious criteria apply.  Documentation on the diagnosis of the 
second primary malignancy must be provided at the time of reporting as a serious adverse event (e.g.,any 
confirmatory histology or cytology results, X-rays, CT scans, etc.).
d. According to local practice hematology tests should be performed for complete blood cell count (CBC) and will 
include red blood cell count (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), white blood cell 
(WBC) count with differential, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet 
count. This information will no longer be collected by Celgene on an eCRF. however the information will continue 
to be recorded in the subjects’ medical records.
e. According to local practice serum chemistry tests should be performed (total protein, albumin, calcium, 
phosphorous, glucose, uric acid, total bilirubin, alkaline phosphatase, AST (SGOT), ALT (SGPT), sodium, 
&(/*(1(35235,(7$5<,1)250$7,21
$7
$7
$7
$7
X
d in 
in the
the subje
subj
records onl
records o
0$
SAEs
SAEs
2
1)
,1
l practice
l practice
,1
,1
,1
,1
X
per local pra
per local pr
5<
X
As per 
As pe
7$
,
5,
5,
5,(
2 5,
partate transa
artate trans
minase; SGPT
inase; SGP
he administra
he adminis
en/done as in
/done as in
xtended Acc
xtended Ac
lenalidomide
lenalidomi
gnancies (SP
gnancies (SP
his includes 
his includes
the study, fro
he study, fr
ts of second 
ts of second 
rtant Medica
nt Medica
d primary ma
primary ma
firmatory his
firmatory hi
According to 
According to 
include red
include red
(WBC)
WBC
oun

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
31
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
potassium, blood urea nitrogen, creatinine and lactate dehydrogenase. This information will no longer be collected 
by Celgene on an eCRF, however the information will continue to be recorded in the subjects’ medical records.
f. For FCBP with regular or no menses and on lenalidomide, pregnancy testing has to occur every 28 days after the 
first 4 weeks of therapy through 28 days following treatment discontinuation. For FBCP with irregular menses 
such testing must happen after the first four weeks of treatment though 28 days following treatment 
discontinuation.
&(/*(1(35235,(7$5<,1)250$7,21

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
32
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
3.
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
1.
STUDY CONTACT INFORMATION .....................................................................3
2.
SYNOPSIS...............................................................................................................4
3.
TABLE OF CONTENTS........................................................................................32
4.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...........................39
5.
INTRODUCTION..................................................................................................43
5.1.
Mantle Cell Lymphoma ..........................................................................................43
5.2.
Background and Rationale for Lenalidomide ..........................................................44
5.2.1.
Preclinical studies with Lenalidomide.....................................................................45
5.2.2.
Clinical Studies of lenalidomide in Non-Hodgkin’s Lymphoma..............................46
5.2.3.
Clinical Studies of Lenalidomide in Multiple Myeloma ..........................................47
5.2.4.
Clinical Studies of Lenalidomide in Myelodysplastic syndromes............................47
5.2.5.
Clinical Studies of Lenalidomide in Chronic Lymphocytic Leukemia.....................48
6.
STUDY OBJECTIVES...........................................................................................49
6.1.
Primary Objective...................................................................................................49
6.2.
Secondary Objectives .............................................................................................49
7.
STUDY ENDPOINTS............................................................................................50
7.1.
Primary...................................................................................................................50
7.2.
Secondary...............................................................................................................50
8.
OVERALL STUDY DESIGN ................................................................................51
8.1.
Design Rationale ....................................................................................................51
8.1.1.
Dose Rationale .......................................................................................................51
8.1.2.
Discussion of Study Design ....................................................................................52
8.1.2.1.
Stratification...........................................................................................................52
8.1.2.2.
Treatment Phase .....................................................................................................54
8.2.
Assessment of Second Primary Malignancies .........................................................57
8.3.
Data Monitoring Committee ...................................................................................58
8.4.
Independent External Pathological Review.............................................................58
8.5.
Independent Review Committee (IRC) ...................................................................59
9.
STUDY POPULATION.........................................................................................60
&(/*(1(35235,
..............
........
.............
.........
..............
.............
DY DESIG
DY DESIG
nale
nale .......
..
ionale
onale .......
ussi
ssion of
on of S
f
tratificat
tratificatioio
Treatme
Treatm
(7$5<,1)250$7,21
39
....... 43
43
...........
.......... 43
4
.............
............
..............
............
.............
............
.............
.............
yndro
yndromes
mes
phocyt
phocytic Le
ic
..............
...
..............
..........
.............
.............
Ass
As
.3.
.3.
.4.
.4.
5,(

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
33
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
9.1.
Patient Inclusion Criteria ........................................................................................60
9.2.
Patient Exclusion Criteria .......................................................................................61
10.
DESCRIPTION OF TREATMENT........................................................................63
10.1.
Treatment Assignments ..........................................................................................63
10.1.1.
Arm A ....................................................................................................................63
10.1.2.
Arm B ....................................................................................................................63
10.1.3.
Dose Modification or Interruption for Lenalidomide - Arm A.................................64
10.1.4.
Dose Modification or Interruption for Investigator’s choice - Arm B ......................69
10.1.5.
Tumor Lysis and Tumor Flare - Lenalidomide........................................................69
10.1.6.
Thromboembolism - Lenalidomide.........................................................................70
10.1.7.
Prior/Concomitant medications and other permitted concomitant therapies.............70
10.1.8.
Prohibited concomitant therapy...............................................................................71
10.2.
Discontinuation from Treatment .............................................................................71
11.
STUDY DRUG MATERIALS AND MANAGEMENT .........................................72
11.1.
Supplier(s)..............................................................................................................72
11.2.
Dosage Form..........................................................................................................72
11.3.
Dosage Regimen.....................................................................................................72
11.3.1.
Lenalidomide..........................................................................................................72
11.3.2.
Investigators Choice ...............................................................................................72
11.4.
Drug Dispensing Requirements...............................................................................72
11.5.
Special Handling Instructions .................................................................................73
11.6.
Treatment Compliance............................................................................................73
11.7.
Packaging and Labeling..........................................................................................73
11.8.
Receipt and Storage................................................................................................73
11.9.
Record of Administration .......................................................................................73
11.10.
Accountability ........................................................................................................74
11.11.
Handling and Disposal............................................................................................74
12.
ASSESSMENT OF EFFICACY.............................................................................75
12.1.
Assessments ...........................................................................................................75
12.2.
Methods and Timing of Efficacy Assessments........................................................75
13.
ASSESSMENT OF SAFETY.................................................................................77
13.1.
Assessments ...........................................................................................................77
13.2.
Methods and Timing of Safety Assessments ...........................................................78
&(/*(1(35235,(7$5<,1)250$7,21
3
......64
.6
..........
.... 69
6
..............
...........
..............
............
nt therapi
nt therapies
e
..............
............
.............
.............
ENT
ENT ......
.
..............
...........
.............
.............
.............
............
..............
..........
.............
..........
ments
ments......
.
ructions
ructions ...
iance
iance......
.
d Labeling
d Labeling
nd Storage
nd Storag
d of Admi
d of Admi
ccountabil
countabil
Handlin
Handlin
ASS
AS
2.1.
2.1.
12.2.
2.2.

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
34
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
13.3.
Recording and Reporting of Adverse Events...........................................................78
15.
STATISTICAL ANALYSES..................................................................................82
15.1.
Study Population Definitions ..................................................................................82
15.1.1.
Intent-to-Treat Population (ITT) .............................................................................82
15.1.2.
Treated Set .............................................................................................................82
15.1.3.
Full Analysis Set (FAS)..........................................................................................82
15.1.4.
As Treated population.............................................................................................82
15.1.5.
Per-protocol Set (PPS)............................................................................................82
15.1.6.
Subgroup analysis...................................................................................................83
15.2.
Efficacy Evaluation ................................................................................................83
15.2.1.
Primary Efficacy Endpoints....................................................................................83
15.2.2.
Secondary Endpoints ..............................................................................................84
15.2.3.
Analysis Methods...................................................................................................88
15.3.
Background and Demographic Characteristics........................................................89
15.4.
Study Drug .............................................................................................................89
15.5.
Concomitant Therapy .............................................................................................89
15.6.
Safety Evaluation....................................................................................................89
15.7.
Interim Analyses.....................................................................................................90
15.8.
Sample Size and Power Considerations...................................................................91
15.9.
Other Topics...........................................................................................................92
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................93
16.1.
Monitoring .............................................................................................................93
16.2.
Audits and Inspections............................................................................................93
16.3.
Investigator(s) Responsibilities...............................................................................93
&(/*(1(35235,(7$5<,1)25
.............
.............
..............
.......
.............
.......
.............
..
..............
........
.............
..........
..............
.............
..............
.............
.............
.............
.............
.............
..............
.........
.............
...........
nd Demogra
d Demogr
g .............
.......
mitant The
ant The
fetet
f y y Evalua
Evalu
Interim A
Interim A
Sam
Sam
.9.
O
16.6
1
50$7,21
7
$7
50$
0$7
250

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
35
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
17.
REGULATORY CONSIDERATIONS...................................................................95
17.1.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................95
17.2.
Protocol Amendments.............................................................................................95
17.3.
Informed Consent ...................................................................................................95
17.4.
Patient Confidentiality............................................................................................96
18.
DATA HANDLING AND RECORDKEEPING.....................................................97
18.1.
Data/Documents.....................................................................................................97
18.2.
Data Management...................................................................................................97
18.3.
Retention of Records ..............................................................................................97
19.
PREMATURE DISCONTINUATION OF THE STUDY .......................................99
19.1.
Single Site ..............................................................................................................99
19.2.
Study as a Whole....................................................................................................99
20.
REFERENCES.....................................................................................................100
21.
APPENDICES......................................................................................................106
21.1.
Adverse Event ......................................................................................................106
21.1.1.
Abnormal laboratory values defined as adverse events..........................................106
21.1.2.
Serious adverse event ...........................................................................................107
21.1.3.
Classification of severity.......................................................................................108
21.1.4.
Classification of Relationship/Causality of adverse events (SAE/AE) to 
study drug.............................................................................................................108
21.1.5.
Duration ...............................................................................................................108
21.1.6.
Action Taken........................................................................................................108
21.1.7.
Outcome...............................................................................................................109
21.1.8.
Monitoring and reporting of adverse events ..........................................................109
21.1.9.
Immediate reporting of serious adverse events......................................................109
21.1.10.
Pregnancies ..........................................................................................................110
21.1.11.
Safety Queries ......................................................................................................110
21.1.12.
Expedited Reporting of Adverse Events................................................................110
21.2.
Declaration of Helsinki.........................................................................................112
21.2.1.
Introduction..........................................................................................................112
21.2.2.
Basic Principles for All Medical Research ............................................................113
21.2.3.
Additional Principles for Medical Research Combined with Medical Care............115
&(/*(1(35235,(7$5<,1)250$7,21
..97
97
........
.......97
97
..............
............ 9
.............
.......
.............
.............
..............
.......
.............
.......
.............
..
..............
........
.............
..........
adverse eve
adverse ev
..............
.............
.............
.............
hip/Causalit
p/Causal
..............
............
.............
.............
..............
...........
..............
.............
ring and rep
ng and rep
mediate rep
mediate rep
Pregnancie
Pregnancie
Saf
Safetet
f y
.12.
.12.
Ex
Ex
21.2.
21.2
.2.1
2 1

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
36
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.3.
ECOG Performance Status Scale ..........................................................................117
21.4.
MCL International Prognostic Index (MIPI) score (Hoster, 2008).........................118
21.5.
Modified International Workshop Response Criteria (Cheson, 1999)....................119
21.6.
Cairo-Bishop Grading System for tumor lysis syndrome (TLS) ............................122
21.7.
Lenalidomide Pregnancy Prevention Plan for Subjects in Clinical Trials................123
21.8.
Lenalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and
Acceptable Birth Control Methods........................................................................123
21.8.1.
Risks Associated with Pregnancy..........................................................................123
21.8.1.1.
Definition of Females of Childbearing Potential ...................................................123
21.8.1.2.
Definition of Females Not of Childbearing Potential.............................................124
21.8.2.
Counseling ...........................................................................................................124
21.8.2.1.
Females of Childbearing Potential ........................................................................124
21.8.2.2.
Females Not of Childbearing Potential..................................................................124
21.8.2.3.
Males....................................................................................................................125
21.8.3.
Contraception .......................................................................................................125
21.8.3.1.
Female Subjects of Childbearing Potential............................................................125
21.8.3.2.
Male Subjects.......................................................................................................126
21.8.4.
Pregnancy Testing ................................................................................................126
21.8.5.
Pregnancy Precautions for Lenalidomide Use........................................................126
21.8.5.1.
Before Starting Lenalidomide ...............................................................................126
21.8.5.2.
During and After Study Participation....................................................................127
21.8.5.3.
Additional Precautions..........................................................................................128
21.9.
Lenalidomide Education and Counseling Guidance Document for Female
Subjects................................................................................................................129
21.9.1.
Female of Childbearing Potential: .........................................................................129
21.9.2.
Female Not of Childbearing Potential (Natural Menopause for at Least 24 
Consecutive Months, a Hysterectomy, or Bilateral Oophorectomy):......................131
21.10.
Lenalidomide Education and Counseling Guidance Document for Male
Subjects................................................................................................................132
21.11.
Lenalidomide Information Sheet............................................................................134
21.12.
EORTC QLQ-C30 Questionnaire .........................................................................136
123
23
......
... 123
123
.............
............12
1
.............
.......
.............
.............
..............
.......
.............
.......
.............
..
..............
........
.............
..........
..............
.............
..............
.............
lido
lidomide
mide U
de
de ..........
.......
y Parti
articipat
cipa
ons
n ........
......
Educat
ducation a
..............
.............
of Childbea
Childbe
alale Not
e Not of
of
onsecut
onsecutive
ive
Lenalid
Lenali
Subj
ubj
.11.
.11.
L
21.12.
21.12.

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
37
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
LIST OF TABLES
Table 1:
Celgene Emergency Contact Information..................................................................3
Table 2:
Schedule of Study Assessments for Arm A and Arm B patients  (28 days = 1 
cycle)......................................................................................................................24
Table 3:
Schedule of study assessments for patients with cross-over on lenalidomide 
after progression in investigator's choice Arm B (28 days = 1 cycle) – No 
more than 10 weeks after last day of last cycle of treatment in Arm B.....................28
Table 4:
Schedule of Study Assessments: Guidance for Extended Access Phase...................30
Table 5:
Abbreviations and Specialist Terms........................................................................39
Table 6:
Overview of dosage of Investigator's choice drugs..................................................64
Table 7:
Dose Modification for Lenalidomide ......................................................................65
Table 8:
Dose reduction steps for Adverse Events related to Lenalidomide for patients 
initiating treatment at 25 mg daily on Days 1-21, every 28 days..............................68
Table 9:
Dose reduction steps for Adverse Events related to Lenalidomide for patients 
initiating treatment at 10 mg daily on Days 1-21, every 28 days..............................68
Table 10:
Confidence Intervals...............................................................................................92
Table 11:
Summary of Modified Response Criteria ..............................................................121
&(/*(1(35235,(7$5<,1)250$7,21
28
28
........30
30
............
............39
3
..............
.............
..............
.........
mide for pati
mide for pati
days
days........
......
nalido
alidomide 
mid
ery
ery 28 days
28 days
y
.............
..........
..............
..........

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
38
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................53
&(/*(1(35235,(7$5<,1)250$7,21

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
39
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
4.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Table 5:
Abbreviations and Specialist Terms
Abbreviation or
specialist term
Explanation
AE
Adverse event
ALC
Absolute lymphocyte count 
ALT (SGPT)
Alanine transaminase (serum glutamic- pyruvic transaminase) 
ANC
Absolute neutrophil count
APC
Activated protein C
AST (SGOT)
Aspartate transaminase (serum glutamic-oxaloacetic 
transaminase)
ASA
Acetylsalicylic acid
ß- HCG
Beta human chorionic gonadotropin
BUN
Blood urea nitrogen
CBC
Complete blood count
CFR
Code of Federal Regulations
CLL
Chronic lymphocytic leukemia
CNS
Central nervous system
CR
Complete response
CrCl
Calculated creatinine clearance
CRu
Complete response unconfirmed
CRF
Case report form
CRP
C-reactive protein
CSF
Cerebrospinal fluid
CT
Computerized Tomography
CTCAE
Common terminology criteria for adverse events
DLT
Dose limiting toxicity
DMC
Data Monitoring Committee
DVT
Deep vein thrombosis
ECG
Electrocardiogram
&(/*(1(35235
culated cre
culated 
35,(7$5<,1)250$7,21
$7
ase)
se)
$7
$7
$7
0$
50
oacetic
acetic
25
)2
pinin
,1
< ,
5<
ulat
ula ions
ns
$5
cy
cytiti
y c leukem
c leuk
7$
ous system
ous system
(
tete response
respons
5,
35
Com
Complete
plete
m
2
Case r
Cas
52
3
C
3
(
1(
(
*
MC
MC
(/
DVT
DVT
&(
&
CG
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
40
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 5:
Abbreviations and Specialist Terms (Continued)
Abbreviation or
specialist term
Explanation
ECOG
Eastern Cooperative Oncology Group
EMEA
European Agency for Evaluation of Medicinal Products
ESMO
European Society for Medical Oncology
FAS
Full Analysis Set
FCBP
Female of childbearing potential
FISH
Fluorescence in situ hybridization
FL
Follicular lymphoma
FDA
Food and Drug Administration
GCP
Good Clinical Practice
G-CSF 
Granulocyte colony-stimulating factor
GM-CSF
Granulocyte-macrophage colony-stimulating factor
HBV
Hepatitis B virus 
HC
Health Canada
HCV
Hepatitis C virus
HIV
Human Immunodeficiency Virus
HR
Hazard Ratio
ICD
Informed Consent Document
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IFN
Interferon
IL
Interleukin
IMiD®
Immunomodulatory drug
IND
Investigational New Drug
INR
International normalized ratio
IRB
Institutional Review Board
IRC
Independent Review Committee
ITT
Intent to treat
IUD
Intrauterine device
&
IRC
IRC
&(/
IRB
IRB
(/*(1(35235,(7$5<,1)250$7,21
$7
$7
$7
$7
0$
50
25
)2
1)
factor
ac
,1
lolony-
ny stimu
tim
<
5<
7$
us
us
(7
mmunodefic
munodefic
5,(
d Ratio
Ratio
35
form
ormed Co
ed Co
23
Internati
Internati
52
3
Inde
nde
35
3
( 3
1(
(1
*(
/*
(/
&(
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
41
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 5:
Abbreviations and Specialist Terms (Continued)
Abbreviation or
specialist term
Explanation
IUS
Intrauterine system
IWRC
International Workshop Response Criteria
LDH
Lactate dehydrogenase
MCL
Mantle cell lymphoma
MCV
Mean corpuscular volume
MDS
Myelodysplastic syndrome
MedDRA
Medical Dictionary for Drug Regulatory Activities
MIPI
MCL International Prognostic Index
MITT
Modified intent to treat
MRI
Magnetic Resonance Imaging
MTD
Maximum tolerated dose
NCI
National Cancer Institute
NHL
Non-Hodgkin’s Lymphoma
NSAIDS
Non-steroidal anti-inflammatory drug
ORR
Overall response rate
OS
Overall survival
PD
Progressive disease
PFS
Progression-free survival
PPS
Per-protocol (Set)
PR
Partial response
PTT
Partial thromboplastin time
PT
Prothrombin Time
QoL
Quality of Life
RDC
Response Determination Committee
RBC
Red blood cell
R-CHOP
Rituximab -Cyclophosphamide, Doxorubicin, Vincristine and 
Prednisolone
R-Hyper CVAD 
Rituximab -Cyclophosphamide Vincristine, Adriamycin and 
Dexamethasone
&
R-
R-CH
CH
&(/*(1(35235,(7$5<,1)250$7,21
$7
$7
$7
$7
0$
50
vit
vities
i
25
)2
1)
,1
<
e
5<
mpho
mphoma
ma
7$
ntiti
n -inflam
inflam
(7
sponse rate
ponse rate
5,(
l survival
l survival
35
rogressive d
gressive 
23
Progress
Progress
52
3
Per-
er
35
3
( 3
1(
(1
*(
C
/*
RBC
RBC
(/
&(
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
42
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 5:
Abbreviations and Specialist Terms (Continued)
Abbreviation or
specialist term
Explanation
RNA
Ribonucleic acid
SAE
Serious adverse event
SD
Stable disease
SOP
Standard Operating Procedure
SPC
Summary of product characteristics
SPD
Sum of the products of the greatest diameter
TCR
Tumor control rate
TFR
Tumor flare reaction
TFT
Thyroid function tests
TLS
Tumor lysis syndrome
TNF
Tumor necrosis factor
TSH
Thyroid stimulating hormone
TTF
Time-to-treatment failure 
TTP
Time to progression
TTR
Time to tumor response
ULN
Upper limit of normal
VEGF
Vascular endothelial growth factor
WBC
White blood cell
WHO
World Health Organization
WMA
World Medical Association
&(/*(1(35235,(7$5<,1)250$7,21
$7
$7
$7
$7
0$
50
25
)2
1)
,1
<
rmone
mone
5<
failure
ailur
7$
ssi
ssion
on
(7
mor respon
mor respon
5,(
limit of no
limit of n
35
ascular end
cular en
23
White bl
White bl
52
3
Wo
Wo
35
3
( 3
1( 3

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
43
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
5.
INTRODUCTION
5.1.
Mantle Cell Lymphoma
Mantle-cell lymphoma (MCL) is a distinct subtype within B-cell type lymphoma originating 
from the mantle zone of the lymph node and is characterized by the overexpression of a member 
of the cyclin D family.  Tumors with overexpression of the cyclin D1 are associated with the 
landmark t (11;14)(q13;q32) chromosomal translocation (Fernandez, 2005). In rare cases, 
overexpression of other cyclin D members is seen (Fu, 2005).  MCL accounts for approximately 
5% of all lymphomas and usually affects predominantly men over the age of 60.  Histologically, 
the MCL cells appear small with features similar to indolent lymphomas.  For this reason, MCL 
was often grouped in the category of indolent lymphoma.  However, the discovery of a 
characteristic chromosomal translocation involving the cyclin D1 gene led to an improved ability 
to diagnose MCL and recognition that most cases had a clinical behavior similar to aggressive 
lymphomas. There is a subgroup of MCL that show an indolent clinical course, and recent gene 
profiling studies in the tumor tissue demonstrated a signature of 13 genes that were 
underexpressed in the indolent tumors when compared to the conventional disease. Notably, 
SOX11 was absent in indolent cases. This was further validated in an independent series of 112 
MCL and lack of SOX11 was associated with increased overall survival (Fernandez, 2010).  In 
addition, several histopathological, cytologic distinct subtypes have been identified, mainly 
based on the growth pattern and type of proliferation: the typical nodular or diffuse proliferation 
of atypical lymphoid cells, and the blastoid variant. The blastoid variant mimics acute 
lymphocytic and follows an aggressive course with a particularly poor prognosis (Schlette, 
2001).
Recent efforts have been made to administer intensive chemotherapy including high-dose 
cytarabine based regimens with rituximab or autologous stem cell transplantation (ASCT) as the 
upfront therapy in younger patients with good performance status. Several randomized and non-
randomized studies have provided evidence that intensive chemotherapy followed by ASCT may 
benefit patients aged younger than 65 years (de Guibert, 2006; Dreyling, 2005; Geisler, 2008). 
The reported 3 year overall survival rates range from 70 to75% and thus are above the reported 
historical median survival data of 3 years. 
Unlike other lymphoma types, there is no clear agreement on the treatment to be used for front-
line therapy.  Most physicians have used rituximab-containing anthracycline-based 
chemotherapy regimens such as R-CHOP, or on high-dose cytarabine regimens such as R-Hyper 
CVAD or R-DHAP. Fludarabine-based regimens are also commonly used, however often in the 
relapsed setting, together with anthracyclines or alkylating agents. The European MCL network 
currently is conducting a randomized phase III trial comparing first line treatment of R-FC with 
R-CHOP.
In patients with mantle cell lymphoma who have relapsed after initial therapy including intensive 
chemotherapy or autologous transplantation, the prognosis is poor and there is no clear 
consensus on how such patients should be treated. One agent, the proteasome inhibitor 
Bortezomib has been approved in the US and other countries for the treatment of 
relapsed/refractory MCL (Fisher, 2006; Kane, 2007). In a single arm phase II study of 155 
patients a response rate of 31% was achieved with duration of 9 months. 
&(/*(1(35235,(7$5<,1)250$7,21
ly 
cally
ally,
n, MCL
MCL
a 
mproved abi
proved abi
r to aggress
r to aggress
se, and rece
se, and rece
that were
that were
nal disease
nal disea
n independ
independ
urvival (
vival (Fe
Fe
have been
have be
ypical
pical
y
n
l odu
odu
blastoid va
lastoid v
particularly
particularly
ntensive ch
ntensive ch
or autologou
r autologou
good perfo
good perfo
idence that 
idence t
65 y
5 ears (
ars (d
vival rates r
ival rates r
ta of 3 y
ta of 3 yea
types, there
types, th
ysicians ha
ysicians 
mens such 
mens such 
AP.
AP. Fl
Fludar
uda
l
ng, togethe
ng, togethe
s conduct
conductinin
P.
P
pati
atients wi
ents wi
chemothera
hemothera
consens
onsen
rte

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
44
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
The main concern with MCL is that relapses occur eventually in most patients and despite initial 
responses, the remission durations are short. Thus, patients need repeated treatment in order to 
control the disease as long as possible. Other agents that have been demonstrated to display 
activity in a variety of B-cell lymphomas are commonly used in relapsed MCL patients. 
Fludarabine single agent induces response rates of 30 – 40% when used in the first-line setting 
and 63% when combined with cyclophosphamide (Foran, 1999; Cohen, 2001). Single agent 
therapy with fludarabine is being used in the relapsed setting once patients have received 
anthracyclines and cytarabine. (Zinzani, 2000; Tobinai, 2006). Gemcitabine as another 
nucleoside analogue has distinct antitumor activity in relapsed MCL (Dumontet, 2001). A single 
center study of 30 patients treated with gemcitabine and dexamethasone showed a response rate 
of 36% (Morschhauser, 2007). Single agent rituximab led to objective antitumor responses in 
22% of the patients with MCL (Ghielmini, 2000). Chlorambucil as a backbone of the treatment 
of intermediate risk and indolent lymphomas is also used in MCL patients (Rai, 2000; Ardeshna, 
2003). Single agent intermediate and high dose cytarabine (2 – 8 g total dose according to the 
UK SPC, 2007 for Cytarabine) has shown activity in relapsed refractory non-Hodgkin’s 
lymphoma when administered at doses of 4 – 8 g/m2 in a 21 to 28 days cycle (Kantarjian, 1983).
However, options are limited for patients with relapsed mantle cell lymphoma and there is a clear 
need for novel innovative approaches. The increasing understanding of the MCL cell biology has 
led to the development of new therapeutic agents with antitumor activity that target crucial 
biological pathways, including cell cycle inhibitors [e.g. flavopiridol], mTOR inhibitors 
[temsirolimus (Hess, 2009), everolimus (Haritunians, 2007)] and histone deacetylase inhibitors. 
These new therapeutic approaches have been studied in patients previously treated with 
aggressive regimens (Kouroukis, 2003; Goy, 2005; O’Connor, 2005). The combination of these 
new therapeutic strategies and the correct stratification of the patients according to the risk may 
ultimately change the management and outcome of MCL patients (Jares, 2008).
5.2.
Background and Rationale for Lenalidomide
Lenalidomide (REVLIMID® Celgene Corp., NJ, USA) is a member of a class of pharmaceutical 
compounds known as immunomodulatory drugs. It offers potential benefit over the first 
commercially available IMiD® compound, thalidomide, in terms of both safety and efficacy in 
patients (Galustian, 2004). Thalidomide has been evaluated in 16 patients with 
relapsed/refractory mantle cell lymphoma patients for antitumor activity in combination with 
rituximab. Thirteen patients (81%) experienced objective response and the estimated 3 year 
survival ws 75% (Kaufmann, 2004).  The key to the therapeutic potential of lenalidomide lies in 
the fact that it has multiple mechanisms of action, which act to produce anti-inflammatory, anti-
angiogenic, and anti-tumor effects. These effects are thought to be contextual in that they depend 
on both the cell type and the triggering stimulus. To date, lenalidomide has been associated with 
TNF-α inhibitory, T-cell co-stimulatory, and anti-angiogenic effects (Galustian, 2004).
Lenalidomide is marketed in the United States, Canada and Argentina for the treatment of 
patients with transfusion-dependent anemia due to low- or intermediate-1-risk Myelodysplastic 
Syndrome (MDS) associated with a deletion 5q cytogenetic abnormality with or without 
additional cytogenetic abnormalities and in combination with dexamethasone for patients with 
previously treated multiple myeloma. Lenalidomide is also approved and marketed in multiple 
&(/*(1(35235,(7$5<,1)250$7,21
ngle
ngle
e rate
e rate
nses in 
in 
e treatment
e treatment
000
00; Ardes
Ardes
ccording to
cording 
n-Hodgkin’
Hodgkin
ycle (
cle (Kanta
K
ympho
mphoma a
ma
ng of the M
g of the M
or activit
or activ y t
vopiridol], 
vopiridol], 
07)] and hi
)] and 
in patients p
n patients 
O’Connor
O’Conno
ication of th
ication of t
me of MCL
me of MCL
onale for L
nale for
ne Corp., N
e Corp., N
odul
dulatory
atory d
y
® com
® compou
pou
m
Thalido
Thalid mi
m
tle cell lym
le cell ly
patients (81
atients (8
(Kaufmann
Kaufmann
has mult
has multipipl
and ant
and anti-i-tutu
he cell t
cell type
ype
α inhibitory
α inhibitory
enalido
nalidomid
mid
pati
pa ents w
nts w
yndro
ndro
y

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
45
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
countries including the US and EU, in combination with dexamethasone, for the treatment of 
patients with multiple myeloma who had been treated with at least one prior therapy.
Lenalidomide is being investigated as treatment for various hematological and oncologic 
indications.  Studies have also been conducted in non-oncologic conditions including complex 
regional pain syndrome. 
5.2.1.
Preclinical studies with Lenalidomide
Lenalidomide displays antiproliferative effects against hematopoietic tumor cells, especially 
those of the B cell lineage, including mantle cell Lymphoma.  A dose-dependent upregulation of 
the p21WAF-1 expression was observed in Namalwa lymphoma- cell line, and in U266- and LP-
1 multiple myeloma cell lines (Verhelle, 2007).  The p21WAF-1 upregulation correlated with 
increased binding to the cyclin dependent kinases CDK2, CDK4 and CDK6 complexes leading 
to decreased retinoblastoma protein phosphorylation and G1/G0 cell cycle arrest (Verhelle, 
2007). These data suggest that the lenalidomide mechanism of action involves upregulation of 
p21WAF-1, which may be in part responsible for the antiproliferative activity observed against 
tumor cells. 
The effect of lenalidomide on proliferation of mantle cell lymphoma, and on the expression of 
several important genes involved in cancer cell cycle, was examined by quantitative real-time 
polymerase chain reaction. As mentioned before, mantle cell lymphoma usually has a t(11;14) 
translocation, resulting in cyclin D1 overexpression. Results indicate that high baseline cyclin D1 
and low p21 gene expression in MCL cell lines correlate with sensitivity to lenalidomide and 
may be predictive of a good clinical response to lenalidomide. In addition, monitoring of SPARC 
expression in MCL patients may enable early identification of patients who are responding to 
lenalidomide therapy. SPARC (osteonectin) is a gene coding for a matrix glycoprotein recently 
proposed to be a potential tumor suppressor and important for the inhibition of erythroid cell 
proliferation by lenalidomide. The level of constitutive cyclin D1 gene expression in MCL cell 
lines correlates with the order of sensitivity to lenalidomide. Conversely, the constitutive p21 
gene expression is inversely proportional to lenalidomide sensitivity. Therefore, the baseline 
cyclin D1 to p21 gene expression ratio could be predictive of patient response to lenalidomide 
therapy. It was also found that lenalidomide markedly increases SPARC gene expression in NHL 
cells in a manner that correlates with the anti-proliferative activity of lenalidomide. The order of 
sensitivity to lenalidomide by various NHL cell lines is Namalwa (Burkitt’s lymphoma)>Rec-
1>Jeko-1>Granta-519>JVM-2 (all MCL)> DB (diffuse large B cell lymphoma). Thus SPARC 
gene induction may be a biomarker of NHL or MCL tumor response to lenalidomide (Zhang, 
2007).
Lenalidomide also enhances T and NK cell stimulation, and augments NK cell-mediated 
hematopoietic tumor cell lysis, which may contribute to its clinical anti-tumor activity. In both 
freshly isolated T cells and in differentiated Th1 cells, lenalidomide enhanced T cell proliferation 
and augmented production of interleukin 2 (IL-2) and interferon % (IFN-%) following T cell 
receptor activation (Corral,1999; Schafer, 2003). Several pre-clinical studies show that the 
mechanism of lenalidomide comprises T cell activation and may involve induction of the Akt 
pathway and AP-1 transcriptional activity. 
The effects of lenalidomide on NK and T cell activity have also been examined. Using NKT 
cells from healthy donors and multiple myeloma (MM) patients, in vitro treatment with 
&(/*(1(35235,(7$5<,1)250$7,21
on of
n of
and LP
nd LP-
ted wi
d with
th
i
lexes leadin
exes leadin
st t (Verhelle
Verhe
es upregula
es upregu
vit
vity observ
y observ
ma, and on t
ma, and on
mined by qu
ined by qu
lympho
lymphoma
m
lts indicate
ts indicate
l
e with sen
e with sen
alido
alidomide. 
mide
ntificat
ntifica ion
s a gene cod
a gene cod
r and impor
and impo
of const
of constitu
tivit
ivity to l
y t
e
rtional to l
rtional to l
n n ratio
ratio cou
cou
at lenalidom
at lenalidom
elates with
ates with
mide by
de b varar
y
19>JVM
9>JVM-2
ay y be a bio
be a bio
mide also en
e also en
opoiet
opoi ic tum
ic tum
hly
hly i
y so
solated
lated
and augmen
nd augmen
receptor 
eceptor 
echa
h

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
46
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
lenalidomide significantly enhanced NKT cell expansion in response to stimulation with 
dendritic cells presenting the NKT ligand α-galactosyl-ceramide. Lenalidomide markedly 
enhanced in vitro NK-cell mediated lysis of both MM cell lines and autologous patient MM 
cells. When the tumor cells were co-cultured with PBMC, lenalidomide enhanced the apoptosis 
of both K562 cells and Raji cells (Zhu, 2008), supporting an NK cell mediated lysis mechanism.
Thus there is direct antiproliferative activity of lenalidomide against hematopoietic tumor cells, 
especially those of the B cell lineage and including MCL, via upregulation of the tumor 
suppressor genes p21 and SPARC. Furthermore, the immunomodulatory effects of lenalidomide 
on T and NK cells, alone and in combination with antibodies such as rituximab, may enhance its 
anti-tumor activity in MCL patients.
Furthermore, recent preclinical studies suggest that lenalidomide may promote restoration of 
anti-tumor immunological effects in patients with certain hematological malignancies.  It was 
reported that patients with CLL have a dysfunction of their T cells (Ramsay, 2008).  When the 
dysfunction was studied using an in vitro system, in which the restoration of the immunologic 
synapse was taken as the functional assay, treatment of both the patient’s T cells and the CLL 
cells was required for synapse formation. It was also reported that the impaired T cell 
immunological synapse formation was seen in both CD4 and CD8 T cells from follicular 
lymphoma (FL) patients compared to age-matched healthy donors (Ramsay, 2009). This defect 
was induced by tumor contact since T cell defects were induced in healthy T cells when they 
were co-cultured for 48 hr with allogeneic FL cells, but not with healthy allogeneic B cells.  In 
co-culture with FL cells, previously healthy T cells showed suppressed recruitment of integrin 
LFA-1, Lck, Itk, Rab27A and filamin-A to the synapse in subsequent T cell: APC interactions. It 
was further demonstrated that the immune synapse defects were repaired in part by treatment of 
the cells with the immunomodulatory drug lenalidomide. Treatment of both FL B cells and 
autologous T cells with lenalidomide (0.5 μM for 24h) was required to enhance formation of the 
F-actin synapse and recruitment of tyrosine-phosphorylated protein and filamin-A irrespective of 
the presence of exogenous antigen. 
Additionally, it was described that lenalidomide up-regulated the expression of genes involved in 
the immune response, such as co-stimulatory and antigen-presenting molecules (Gaidarova, 
2008). Furthermore, lenalidomide treatment induced actin cytoskeleton reorganization and 
polarization of MCL cells as early as 30 min, prior to a detectable increase of CD1c expression 
and could be responsible for re-localization of CD1c protein to polarized sites at the plasma 
membrane. Lenalidomide had similar effects on γδT cells, inducing actin cytoskeleton dynamics 
and polarization within minutes in these cells. Lenalidomide enhanced the number of γδT-MCL 
immune synapses and the lytic activity of γδT cells against the tumor cells. 
These laboratory observations of direct lenalidomide effects on tumor cells, in inducing the 
expression of potential tumor suppressor genes and proteins potentially involved in tumor cell 
recognition by T cells, as well as cellular lenalidomide effects on the host immune cells 
potentially to improve tumor cell recognition, serve as the scientific basis for the clinical 
approach described in the clinical trial protocol.
5.2.2.
Clinical Studies of lenalidomide in Non-Hodgkin’s Lymphoma
Three phase 2 studies of single-agent lenalidomide have been conducted in patients with 
relapsed/refractory NHL (CC-5013-NHL-001 in indolent NHL and CC-5013-NHL-002 and 
&(/*(1(35235,(7$5<,1)250$7,21
e
ce its
e its
ration of 
ation of 
cies.  It 
ies.  It wa
wa
008
08).  When
).  Wh
f the immun
f the immu
T cells and
T cells
impaired T
impaired T
T cells
cells fro
fr m
rs (
rs (Ram
R
say
say
ed in healt
ed in hea h
t with healt
with hea
wed suppre
wed suppr
pse in subse
se in sub
e defects w
e defects 
lidomide. 
idomide.
M for 24h) 
M for 24h)
ne
ne-phospho
phospho
lenalido
lenalidom
co-sts imulat
imulat
omide treat
omide tre
s as early a
s as earl
ble for re
le for r -lol
omid
mide had 
e had
wi
with
th
i in 
in min
mi
pses and th
pses and th
boratory
atory ob
ob
y
sio
sion of pot
n of pot
ogni
gnititi
i on by
on by
potenti
otentially
ally
approach
pproa

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
47
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
NHL-003 in aggressive NHL).  The dose/regimen used in these studies was 25 mg p.o. once 
daily for 21 days (D1 – D21) in 28 day cycle, for maximum of either 52 weeks (NHL-001 or 
NHL-002) or until disease progression (NHL-003).  Patients with mantle cell lymphoma were 
included in NHL-002 and NHL-003.  
In the two phase 2 clinical studies that include aggressive histologies (including MCL, DLBCL, 
transformed and FL grade 3), the overall response rate (ORR) was 35% in NHL-002 and 36% in 
NHL-003, respectively (Wiernik, 2008). In NHL002, fifteen of 49 patients had MCL with a 
median duration of disease of 5.1 years and a median of 4 prior treatments before enrollment. In
these MCL patients an ORR of 53% was demonstrated. Three patients (20%) had a CR or 
unconfirmed CR, and 5 patients (33%) had a PR. The median duration of response was 13.7 
months and median PFS was 5.6 months. The most common grade 4 adverse event was 
thrombocytopenia (13%) and the most common grade 3 adverse events were neutropenia (40%), 
leucopenia (27%), and thrombocytopenia (20%). (Habermann, 2009). In the second study (NHL-
003) which was initiated in November 2006, 217 patients were enrolled. In the 57 MCL patients 
who were evaluable for response assessment, lenalidomide therapy led to an objective response 
rate of 42% (25/57). Median progression-free survival (PFS) was 5.7 months. Overall, the 
primary side effect of lenalidomide was reversible myelosuppression. Grades 3 or 4 neutropenia 
occurred in 41%, thrombocytopenia in 19%, anemia in 9.2%. Grade 3 and grade 4 febrile 
neutropenia occurred in only 2% of patients (Witzig, 2011).
5.2.3.
Clinical Studies of Lenalidomide in Multiple Myeloma
Two pivotal multicenter, randomized, placebo-controlled studies comparing lenalidomide plus 
dexamethasone to dexamethasone in relapsed or refractory patients determined that combination 
therapy with lenalidomide and high-dose pulse dexamethasone is significantly more effective 
than high-dose pulse dexamethasone therapy alone as judged by time to progression (TTP), 
progression free survival (PFS), time to –treatment failure (TTF), and the proportion of patients 
who responded to therapy (MM-009 and MM-010) (Dimopoulos, 2007; Weber, 2007).. In both 
trials, superior response rates (61% vs. 19.9 % in MM-009 [p < 0.001] and 60.2% vs. 24% in 
MM-010 [p <0.001]) and greater median times to progression (11.1 vs. 4.7 months in MM-009 
[p < 0.001] and11.4 vs. 4.7 months in MM-010 [p < 0.001]) were achieved by patients who were 
treated with the combination of lenalidomide and dexamethasone compared to patients who 
received placebo plus dexamethasone. Moreover, patients in the lenalidomide plus 
dexamethasone treatment group had a significant survival advantage compared to the placebo 
plus dexamethasone group (p < 0.001 and p = 0.03 in MM-009 and MM-010, respectively).
5.2.4.
Clinical Studies of Lenalidomide in Myelodysplastic syndromes
Lenalidomide has been investigated in patients with MDS in three phase 2 studies for the 
treatment of patients with transfusion-dependent anemia due to Low-or Intermediate-1-risk 
myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or 
without additional cytogenetic abnormalities.  In MDS, lenalidomide was studied at the 
dose/regimen of 10 mg daily (CC-5013-MDS-002/CC-5013-MDS-003) until disease 
progression. Results from the CC-5013-MDS-003 study, in MDS with an associated del 5 (q31-
33) cytogenetic abnormality, showed transfusion independence in 67 % of the patients.  Median 
duration from the date when red blood cell (RBC) transfusion independence was first declared 
(the last day of the 56-day RBC transfusion-free period) to the date when an additional 
&(/*(1(35235,(7$5<,1)250$7,21
n
3.7 
.7 
s s
openia (40%
openia (40%
ond study
ond study (
he 57 MCL 
he 57 MCL
an objectiv
n objectiv
ont
onths. Ove
hs. Ov
n. Grades 3 
Grades 3
de 3 and gr
e 3 and g
e Myelom
e Myelom
olled studie
lled studie
efractory
efractory pa
p
y
dexametha
dexameth
y alalone as j
one as j
treatm
reatment f
ent f
nd MM
d MM-010
01
vs. 19.9 %
s. 19.9 %
median tim
median ti
onths in MM
onths in M
n of lenali
n of lenal
examethaso
exametha
ment group
ment grou
ne group (p
e group (p
Clinical Stu
Clinical Stu
mide has b
e has 
ment of pati
ent of pati
yelodysplas
lodysplas
wi
with
th
i outut ad
ad
dose/reg
dose/re

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
48
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
transfusion was received after the 56-day transfusion-free period among responders was 44 
weeks.  Cytogenetic response was achieved in approximately 75 % of patients. Grade 3/4 
neutropenia and thrombocytopenia are the most common AEs associated with the use of 
lenalidomide, but are manageable with dose reductions and/or interruptions (List, 2006).
5.2.5.
Clinical Studies of Lenalidomide in Chronic Lymphocytic Leukemia 
Lenalidomide monotherapy has been investigated in two investigator initiated trials (IIT) in 
patients with relapsed/refractory CLL (Chanan-Khan, 2006) (Chanan-Khan, 2007), (Ferrajoli, 
2008).  In one study patients with relapsed/refractory CLL were treated with lenalidomide at 
25mg x 21 d q 28 days (Chanan-Khan, 2006) (Chanan-Khan, 2007).  Results from this study 
showed an overall response rate of 53% with 18% of patients achieving a CR and 36% achieving 
a PR.  The median PFS time is 19.4 months (1.2 – 38+ months).  Fatigue (83%) and flare 
reaction (tender swelling of lymph nodes and/or rash) (58%) were the most common non-
hematologic AEs reported. Other important AEs reported were tumor lysis syndrome (5%); 
Grade 3 and 4 thrombocytopenia (45%), and Grade 3 and 4 neutropenia (70%).  Pulmonary 
embolism was reported in two patients (5%).  In the second IIT study (Ferrajoli, 2008), 
continuous dosing of lenalidomide was investigated in patients with relapsed/refractory CLL.  
Lenalidomide was administered daily for 28 days of 28-day cycles until disease progression.  An 
overall response rate of 32% was observed with 3 CR (7%), 1 nodular PR (2%), 10 PR (23%). 
Myelosuppression was the most common toxicity observed, 41% # Grade 3 neutropenia and 
16% Grade 3 thrombocytopenia.  
&(/*(1(35235,(7$5<,1)250$7,21
udy
dy
 achieving
achieving
d flare
d flare
mo
mon non
n non-
ndro
ndrome (5%
me (5
0%).  Pulm
0%).  Pulm
Ferrajo
rrajoli, 20
li,
elelapsed/ref
apsed/re
s unt
u
il disea
l dise
nodular PR 
odula
41%
41% # Gra
Gr
5<

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
49
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
6.
STUDY OBJECTIVES
6.1.
Primary Objective
!
To compare the Progression Free Survival (PFS) of lenalidomide monotherapy versus 
investigator’s choice single agent in patients with mantle cell lymphoma (MCL) who 
are refractory to their regimen or have relapsed once, twice or three times.
6.2.
Secondary Objectives
!
To determine the overall response rate (ORR) of lenalidomide monotherapy or 
investigator’s choice single agent in patients with relapsed or refractory MCL.
!
To evaluate the safety of lenalidomide monotherapy or investigator’s choice single 
agent in patients with relapsed or refractory MCL.
!
To determine the time to progression, and overall survival of patients with relapsed or 
refractory MCL who have received treatment with lenalidomide or of investigator’s 
choice single agent.  
!
To investigate the health-related quality of life (QoL) of patients treated with 
lenalidomide or investigator’s choice single agent treatment.
 
&(/*(1(35235,(7$5<,1)250$7,21
L.
L
hoice
hoice single
single
titients wi
ents with
th
i h
de or of in
de or o
of patients 
f patients 
reatm
eatment.
en
(7$
(7$
35
235

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
50
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
7.
STUDY ENDPOINTS
7.1.
Primary
!
Progression free survival defined as the time from randomization to the first 
observation of disease progression or death due to any cause. If the patient has not 
progressed or died, PFS will be censored at the time of last completed assessment 
when the patient was known not to have progressed. Patients who will receive a new 
treatment without documented progression will be censored at the last assessment 
date that the patient is known to be progression-free.
7.2.
Secondary
!
Overall response rate (complete response [CR], complete response unconfirmed 
[CRu], and partial response [PR]) assessed by a modification of the International 
Workshop Response Criteria IWRC (Cheson, 1999)
!
Duration of response
!
Tumor control rate (Rates for CR, CRu, PR, and stable disease [SD])  
!
Time to progression
!
Time to treatment failure
!
Time to tumor response
!
Overall survival (OS)
!
Safety
!
Quality of Life (EORTC QLQ-C30) 
&(/*(1(35235,(7$5<,1)250$7,21
confirmed 
confirmed 
Internatio
Internati
disease [SD
disease [S
Q-C30
C30) ) 

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
51
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
8.
OVERALL STUDY DESIGN
8.1.
Design Rationale
This study is designed to evaluate the efficacy and safety of lenalidomide therapy versus 
investigator’s choice in patients with relapsed and refractory mantle cell lymphoma. The primary 
efficacy objective is based on PFS. 
The multicenter nature of the study provides assurance that the results are likely to have general 
applicability. Patient eligibility criteria are consistent with those used in studies of this 
population. Patients are required to have measurable disease to facilitate the accurate assessment 
of response, the secondary efficacy endpoint. The International Workshop Response Criteria 
(IWRC) selected (Cheson, 1999) provides an international standard for the assessment of 
lymphoma. Minor modifications to the IWRC will be made to account for differences in the 
evaluation of response in mantle cell lymphoma, such as the evaluation of extranodal disease
(Kane, 2007; Fisher, 2006).  The use of this tool will ensure that data across centers are evaluated 
consistently. Safety will be assessed by evaluating AEs and laboratory data. Adverse event and 
abnormal laboratory value severity will be graded using version 3.0 of the National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Monitoring for 
tumor flare and tumor lysis syndrome will be performed along with safety measures that are 
routinely assessed in investigational studies of hematologic malignancies. Tumor flare reaction 
and tumor lysis syndrome will be recorded as AEs.
Extended Access Phase:
Following the approval of Protocol Amendment #6 an Extended Access Phase will be made 
available for subjects on study treatment in countries where lenalidomide is only available under 
a clinical trial protocol as post-trial access.
These subjects will have a “discontinuation from treatment” visit assessment prior to being 
transferred to the Extended Access Phase
Following the approval of Protocol Amendment #6, subjects on study treatment will be 
considered to have entered the study Extended Access Phase. Study visits and serial 
measurements of safety should continue to be performed as per guidance outlined in Table 4.
Subjects may remain on study until progressive disease or withdrawal for other reasons. Only 
serious adverse events (SAEs) including second primary malignancies (SPMs), and drug 
accountability record information will be collected and reported to Celgene for these subjects.
Follow-up survival data will no longer be collected by Celgene for these subjects.
The Extended Access Phase will end for ongoing subjects still on lenalidomide treatment as soon 
as lenalidomide can be accessed in the commercial setting.
8.1.1.
Dose Rationale
The dose selected (25 mg [p.o.] once daily for 21 days (D1 – D21) in each 28 day cycle) has 
shown activity in three studies in NHL utilizing lenalidomide and is also the approved dose
schedule when used in combination with dexamethasone for patients with multiple myeloma 
who have been treated with at least one prior therapy.  
&(/*(1(35235,(7$5<,1)250$7,21
sment 
sment 
riteria
iteria
nt of 
nt of 
nces in the
ces in the
anodal dise
nodal di
centers are
centers ar
ata. Advers
ta. Adv
f the Nation
f the Natio
CTCAE). M
CTCAE).
wit
with safet
h s
y
malignancie
malignanc
6 an Exten
6 an Exte
ntries whe
ntries whe
ioion from tr
from
hase
hase
olol Amendm
Amend
l
e study
e study Ext
Ex
y
oululd contin
d contin
n study
n stud un
un
y
nts (SAEs) 
s (SAEs)
cord 
cord inform
inform
rvival data w
ival data
nded Acces
ed Acces
ido
id mide c
mide c
1.1.
1.1.
D
The dos
The do
w

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
52
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
8.1.2.
Discussion of Study Design
This is a multicenter, randomized, open-label, comparative controlled phase II study to 
determine the efficacy and safety of single agent lenalidomide over a concurrent control group 
treated with an investigator’s choice single agent in patients with mantle cell lymphoma who are 
refractory to their regimen or have relapsed once, twice or three times (Figure 1). The study aims 
to compare the PFS of lenalidomide therapy over a single agent of investigator’s choice. 
The investigator’s choice in the control arm comprises the monotherapy treatment with one of 
the following: chlorambucil, cytarabine, rituximab, fludarabine, or gemcitabine. The investigator 
shall choose the single agent of choice in the control arm for each patient prior to randomization 
on to the study. Patients in the investigator’s choice arm will have the option to switch to 
lenalidomide at time of progressive disease.
8.1.2.1.
Stratification
Patients will be stratified according to:
!
Time since diagnosis (<3 years or ≥ 3 years)
!
Time since last treatment (<6 months [refractory] or ≥ 6 months)
!
Prior stem cell transplant (yes or no)
Treatment and clinical characteristics will be assessed at screening/baseline, but not used for 
stratification, and will be used within an exploratory analysis:
!
Number of prior treatment lines (with description of treatment regimens, including 
first line treatment and stem cell transplant)
!
MCL International Prognostic Index (MIPI) score at time of diagnosis, if available
!
MIPI score at randomization
!
Ki-67 index (as defined by Determann et al, 2008) in the original pathology specimen 
at diagnosis, if available, or at time of relapse
!
Age and gender
!
Absolute lymphocyte counts at baseline
!
Time since last rituximab dose to cycle 1 day 1   
This study will be conducted in three phases as shown below in Figure 1: Screening phase, 
Treatment phase, and Follow-up phase. 
&(/*(1(35235,(7$5<,1)250$7,21
ator 
or
atioion n 
o
6 m
 months)
onths)
creening/ba
creening/b
alysis:
alysis:
escription o
escription 
splant)
splant)
ndex (MIPI
dex (MIPI
by Determ
eterm
ble
ble, or at ti
, or at t
mphocy
mphocyte c
te
y
nce last ritu
e last ritu
l be condu
l be cond
phase, and
phase, and

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
53
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Figure 1:
Overall Study Design
Following the approval of Protocol Amendment #6 an Extended Access Phase will be made available for subjects on 
study treatment in countries where lenalidomide is only available under a clinical trial protocol as post-trial access.
RELAPSED /
REFRACTORY MCL
RANDOMIZATION
(Treatment start [Cycle 1 Day 1] within 
4 days after randomization)
ARM A: Lenalidomide 25 mg daily on Days 1-
21 every 28 days (28-day cycle)
N=166
ARM B: Single agent investigator’s choice 
(Chlorambucil, Rituximab, Cytarabine, 
Gemcitabine, or Fludarabine)
N=84
Discontinuation of 
treatment due to 
progressive disease or 
relapse
Discontinuation of treatment 
due to reasons other than 
progressive disease or 
relapse (i.e. toxicity)
Discontinuation of 
treatment due to 
progressive disease or 
relapse
Follow up (clinic visit and 
CT scanMRI)
every 56 days ± 7 days 
up to 6 months from the 
start of study drug then 
every 90 days ± 15 days 
thereafter.
Follow up (clinic visit or 
documented telephone 
contact) 
every 90 days ± 15 days
Option to enter into 
Lenalidomide Crossover 
Phase
Lenalidomide 25 mg daily on Days 
1-21 every 28 days (28-day cycle)
Follow up (clinic visit or 
documented telephone 
contact) 
every 90 days ± 15 days
Discontinuation of treatment due to 
progressive disease or relapse
Follow up (clinic visit or 
documented telephone contact) 
every 90 days ± 15 days
STUDY INCLUSION/ 
SCREENING
(Within 28 days of 
randomization)
Discontinuation of treatment 
due to reasons other than 
progressive disease or 
relapse (i.e. toxicity)
Discontinuation of treatment due to 
reasons other than progressive disease 
or relapse (i.e. toxicity)
Follow up (clinic visit and CT scan) 
every 90 days ± 15 days from the start of 
lenalidomide cross-over treatment
Follow up (clinic visit and CT 
scan/MRI) 
every 56 days ± 7 days up to 6 
months from the start of study 
drug then every 90 days ± 15 
&(/*(1(35235,(7$5<,1)250$7,21
1
$5
,1)250
1)250
gator’s choice 
, Cytarabine
r Fludarabine)
N=84
$5<,1
tion of 
tion of 
nt 
nt due to
due
sive 
ve disease o
disease
relapse
relapse
35
hen
en 
5 days 
5 days 
er.
5,(7$
5,(7$
ption to
Lenal
3523
3523
Lenalidom
1-21 
1(3
Discontinuat
Disco
progres
progres

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
54
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Screening Phase
Patients will be screened for protocol eligibility within 28 days prior to randomization as 
outlined in Table 2: Schedule of Study Assessments. Screening/baseline assessments will begin 
once the patient has accepted and signed the informed consent form. CBC and serum chemistry 
tests will be required within 7 days of first dose of study drug. Serology, for HBV (at least 
HBsAg, anti-HBs and anti-HBc) and for HCV will be required as screening assessment within 
28 days of randomization in endemic areas. Eligibility for the study is based on the local 
assessments (CBC, chemistry and serology as well as the local results of the archival tumor / 
lymph node biopsy) done during the screening/baseline phase of the study. 
Confirmation of mantle cell lymphoma diagnosis by the central pathology is not required before 
randomization or treatment start, but will be performed centrally at a later stage.  Eligibility for 
the study is based on assessment of the local pathology results by the investigator. Diagnosis 
based on needle aspirations are not considered acceptable pathologic data for entry in this study. 
The confirmation material submitted for Central Pathology Review must include a biopsy-
proven mantle cell lymphoma specimen, including overexpression of cyclin D1 by 
immunohistochemistry. In patients whose tumors are negative for Cyclin D1 overexpression, 
evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable. 
Tumor / lymph node biopsy specimen, which may be archival slides from specimen obtained at 
the time of initial diagnosis, with representative stained slides supporting the diagnosis of mantle 
cell lymphoma (H&E or Giemsa staining and Cyclin D1 staining), must be sent as soon as 
possible to central pathology before randomization but at the latest 8 weeks after randomization. 
It is highly recommended to submit also the original paraffin block (called tumor block) which 
will be returned to the original institution. If the tumor block cannot be sent, 4-5 additional 
unstained slides must be submitted. If such archival tissue is not available for submission, then a 
re-biopsy is required.
The translocation t(11;14)(q13:q32) by FISH is optional and is not sufficient as sole proof for 
diagnosis. Evidence of the translocation t(11;14)(q13:q32) by FISH can be submitted using the 
original slide or the corresponding confirming photographies. If available, it is also 
recommended to send, for central pathology review, slides containing immunostaining for CD3, 
CD5, CD 10, CD23, CD20, BCL2, Ki-67.
Furthermore, it is highly recommended to perform an unilateral bone marrow biopsy at 
screening, and to send the tumor block to Central Pathology for review at the latest 8 weeks after 
randomization.
 
During the screening/baseline phase, the investigator must allocate one of the “investigator’s 
choice” options to the patient prior to the randomization.
8.1.2.2.
Treatment Phase
Once all eligibility criteria are met and baseline assessments completed, patients will be 
randomized 2:1 to receive lenalidomide monotherapy or the investigator’s choice. The first 
treatment dose of the first cycle administered to the patient is called C1D1. Treatment should 
&(/*
ing the scre
ng the scre
ho
hoice” opti
ice” opt
.1.2.2
1.2.2
*(1(35235,(7$5<,1)250$7,21
d befor
d before
gibilit
gibility y fofor
 Diagnosis
Diagnosi
ntry
ntry i
y n this
n th
nclude a bio
clude a bio
yclin D1 by
in D1 
yclin D1 ov
clin D1 ov
emistry
mistry wi
w
y
slides from
slides fr
des support
es suppo
 staining), 
 staining)
ut at the lat
ut at the lat
nal paraffin
nal paraffin
tum
tumor bl
or blo
rchival t
rchival tiss
iss
by
by FISH i
FISH
y
s
ation t(11;
on t(11;
ing confirm
ng confirm
entral patho
entral patho
0, BCL2
BCL , K
hly
hly reco
rec mm
m
end the tum
end the tum
*(
/*(

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
55
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
start as soon as possible after randomization, but maximum time between randomization and 
C1D1 is 4 days, once the patient has fulfilled the requirements of the Lenalidomide pregnancy 
prevention program (see Section 21.7). Patients will continue in the treatment phase until disease 
progression, unacceptable toxicity or voluntary treatment withdrawal. Toxicity will be assessed 
using the NCI CTCAE criteria version 3 and the dose of lenalidomide or the investigators choice 
single agent will be reduced accordingly (see Table 8 and Table 9 for dose reductions).
Serial assessments of safety and efficacy (CT scans with contrast or MRI with contrast every 56 
days ± 7 days for the first 6 months and then every 90 days thereafter) will be performed as 
outlined in the Schedule of Study Assessments or as directed in the dose modification section.  
Patients may continue participation in the treatment phase of the study until disease progression 
or unacceptable toxicity or voluntary patient withdrawal from treatment, at which point, the 
patients will enter the follow-up phase.
Diagnostic imaging results (CT scan with contrast or MRI with contrast, if CT scan is 
contraindicated) will be reviewed locally and also submitted for central review.
CT scans is the preferred procedure. If CT is contraindicated, MRI is acceptable. It is advised to 
stick to the same procedure for a given patient throughout the study.
 
 
 
Patients who withdraw consent for treatment will continue to be followed for safety, efficacy 
(disease progression), second primary malignancies, and for survival.
Cross over (for patients in the investigators choice Arm B only): 
Patients in the investigator’s choice Arm B, who have documented progressive disease will have 
the option to receive single agent lenalidomide treatment. Patients will undergo baseline 
assessments as outlined in the schedule of assessments of Table 3 for Cycle 1 Day 1.
Treatment with lenalidomide will start as soon as recovery from toxicities of prior treatments of 
Arm B have resolved and all inclusion/exclusion criteria are met (i.e. laboratory parameters), but 
no longer than 10 weeks after last day of last treatment cycle in Arm B.
Assessments during treatment with lenalidomide will be for safety, response evaluation, second 
primary malignancies, and overall survival follow-up. CT scans with contrast/MRI with contrast 
are recommended to be performed every 90 days (± 15 days) until disease progression or 
treatment discontinuation for any other reason (i.e. toxicity). Once a patient experiences disease 
progression or relapse or a patient has stopped treatment for other reasons the patient will enter 
the follow-up phase. In the follow-up phase for patients with progressive disease only 
assessments for safety (including second primary malignancies) and overall survival will be 
done. For patients who have entered the follow-up phase due to treatment discontinuation for 
other reasons additional CT scans with contrast /MRI with contrast will be performed at pre-
defined intervals and assessments for safety (including second primary malignancies) and overall 
survival will be done. Patients will be followed until either 70% of the patients have died or the 
&(/*(1(35235,(
will contin
will contin
lignancies,
lignancies,
stigators ch
stigator
ce
ce Arm
r
A
B
m
entnt lelenalido
nalido
he schedule
he schedu
mide will 
mide will
and all inc
and all in
weeks
weeks afaftete
f
during trea
during trea
alignancies
lignancies
ommended 
mmended 
me
mentnt discon
disco
rogression o
rogression o
the follo
llow
ssessm
ssessm
7$5<,1)250$7,21
n.  
n.  
ressi
ession 
on 
nt, the
t, the
scan is
scan is
ew.
ew
ceptable
ptable. It
< ,1
5<
$5<
(7$
,(7

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
56
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
median follow-up in responding patients is > 2 years or the median duration of response (overall 
response and CR/CRu) has been reached, or four years from last patient randomized, whichever 
comes later, at which time subjects on study treatment will be transferred to post-trial access in 
the commercial setting. 
Follow-up Phase
Subjects withdrawn for any reason from the Extended Access Phase will not participate in a 
study follow-up phase. At their next visit 28 days later any SAEs experienced during this time 
window will be reported via the standard post-marketing process.
Once a patient experiences disease progression or relapse or a patient has stopped treatment for 
other reasons, the patient will enter the follow-up phase.  
!
All patients who discontinue treatment in either study arm or cross-over treatment 
will undergo a safety follow-up visit 28 days after last dosing day for assessment of 
adverse events (including via a physical examination), lenalidomide counseling and 
for a medically supervised pregnancy test for FCBP in Arm A and in cross over as 
specified in Section 21.7 . Vital signs, CBC with differential, and serum chemistry are 
to be performed as clinically indicated. A 28-day safety follow-up assessment will not 
be required either for subjects transferred to post-trial access in the commercial 
setting or to the Extended Access Phase. These subjects will have a “discontinuation 
from treatment” visit at the end of their 7 day rest period from their last on-study 
treatment cycle. At this “discontinuation from treatment” visit commercial 
lenalidomide will be dispensed to the subject. Between this visit and 28 days after, if 
a patient experiences a SAE, this SAE will be reported via the standard post 
marketing process. A pregnancy test should be performed 28 days post treatment 
discontinuation visit.
!
Patients who discontinue treatment due to progressive disease or relapse:
∀
Should be followed by clinic visit or documented telephone contact every 90 days 
(± 15 days) for survival, second primary malignancies and for the first subsequent 
antilymphoma therapy (including the time of and best response to the first 
antilymphoma treatment regimen utilized after discontinuation from treatment in 
this study).
!
Patients who discontinued treatment due to reasons other than progressive disease 
or relapse:
∀
Clinic visits should occur every 56 days to assess disease status (physical exam) 
until disease progression or relapse
∀
CT scan with contrast/MRI with contrast should occur every 56 days (± 7 days)
up to 6 months from the start of study drug then every 90 days ± 15 days
thereafter until disease progression or relapse 
∀
After disease progression or relapse has occurred, patients should be followed by 
clinic visit or documented telephone contact every 90 days (± 15 days) for 
survival, second primary malignancies and for the first subsequent antilymphoma 
&(/*(1(35235,(7$5<,1)250$7,21
ent for 
nt for 
r treatment
treatmen
r assessme
r assessm
de counsel
e couns
and in cro
and in cro
l, and seru
l, and ser
follo
llow-
w-up a
up a
access in t
ccess in 
bjects will h
bjects wil
est peri
t period f
od 
m treatmen
treatme
ect. Betwe
ect. Betw
will
wil be rep
be rep
t should be
should b
atment 
tment due
du
by clinic vi
y clinic v
rvival
rvival, seco
, sec
therapy (in
therapy (i
ma treatme
a treatme
y).).
y
who discon
ho discon
lapse
lapse:
Clinic v
Clinic v
unt
until 
il
∀
C

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
57
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
therapy (including the time of and best response to the first antilymphoma 
treatment regimen utilized after discontinuation from treatment in this study).
∀
Patients in the follow-up phase who withdraw consent for efficacy (disease 
progression) follow-up will continue to be followed for second primary 
malignancies and for survival. A full consent withdrawal must be documented to 
disallow survival follow up.
The follow up phase will continue until either 70% of the patients have died or the median 
follow-up in responding patients is > 2 years or the median duration of response (overall 
response and CR/CRu) has been reached, or four years from last patient randomized, whichever 
comes later, at which time the follow-up study phase will be closed.
Extended Access Phase
Following the approval of Protocol Amendment #6 an Extended Access Phase will be made 
available for subjects on study treatment in countries where lenalidomide is only available under 
a clinical trial protocol as post-trial access.
These subjects will have a “discontinuation from treatment” visit assessment prior to being 
transferred to the Extended Access Phase
Following the approval of Protocol Amendment #6, subjects on study treatment will be 
considered to have entered the study Extended Access Phase. Study visits and serial 
measurements of safety should continue to be performed as per guidance outlined in Table 4. 
Subjects may remain on study until progressive disease or withdrawal for other reasons. Only 
serious adverse events (SAEs) including second primary malignancies (SPMs), and drug 
accountability record information will be collected and reported for these subjects. Follow-up 
survival data will no longer be collected by Celgene for these subjects.
The Extended Access Phase will end for ongoing subjects still on lenalidomide treatment as soon 
as lenalidomide can be accessed in the commercial setting.
8.2.
Assessment of Second Primary Malignancies
Second primary malignancies will be monitored as events of interest and must be reported as 
serious adverse events regardless of the treatment arm the subject is in (see Section 21.1.9).  This 
includes any second primary malignancy, regardless of causal relationship to study drug 
(lenalidomide or Investigator Choice arm drugs), occurring at any time for the duration of the 
study, from the time of signing the ICD through follow-up for overall survival. The Follow-Up 
Phase involves patient contact every 90 days (± 15 days) until patient death or until either 70% 
of the patients have died, or the median follow-up in responding patients is > 2 years, or the 
median duration of response (overall response and CR/CRu) has been reached, or four years 
from last patient randomized, whichever comes later. at which time the follow-up study phase 
will be closed.
Second primary malignancies (SPMs) will continue to be reported for subjects included in the 
Extended Access Phase.
hever 
ver 
will be mad
will be m
only 
nly availa
avail
essment pri
ssment pri
on study
n study tre
y
se. Study
. Study vivi
y
d as per gui
as per gu
ase or with
ase or wi
primary
rimar m
y
a
ected and re
cted and re
Celgene fo
Celgene fo
or ongoing 
ongoing
he co
he commer
mm
Second Pr
Second Pr
cies will be
es will be
regardless o
regardless
primary
primary m
y
Investig
Investigato
ato
time o
time of f si
ves patient
ves patient
tients have
nts hav
an duration 
n duration 
m last pati
last pati
will be clos
will be clo
econd
econd

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
58
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
8.3.
Data Monitoring Committee
An independent external Data Monitoring Committee (DMC) will review ongoing safety data 
throughout the study and efficacy for futility at a pre-defined time point. Specifics are outlined in 
the DMC charter. The first safety analysis will occur after the first 40 patients have received at 
least 2 cycles of treatment or have discontinued prior to completing 2 cycles.  The second safety 
analysis as well as an efficacy analysis for futility will occur after 80 patients complete 2 cycles 
or withdraw before completing 2 cycles. A third safety analysis will occur after 120 patients 
complete 2 cycles or withdraw before completing 2 cycles. A fourth safety analysis will occur
after 200 patients complete 2 cycles or withdraw before completing 2 cycles.
8.4.
Independent External Pathological Review
An independent central pathologist will review the lymph node/tumor biopsy for retrospective 
confirmation of the diagnosis of mantle cell lymphoma. 
The confirmation material submitted for Central Pathology Review must include a biopsy-
proven mantle cell lymphoma specimen, including overexpression of cyclin D1 by 
immunohistochemistry. In patients whose tumors are negative for Cyclin D1 overexpression, 
evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable. 
Tumor / lymph node biopsy specimen, which may be archival slides from specimen obtained at 
the time of initial diagnosis, with representative stained slides supporting the diagnosis of mantle 
cell lymphoma (H&E or Giemsa staining and Cyclin D1 staining), must be sent as soon as 
possible to central pathology before randomization but at the latest 8 weeks after randomization. 
It is highly recommended to submit also the original paraffin block (called tumor block) which 
will be returned to the original institution. If the tumor block cannot be sent, 4-5 additional 
unstained slides must be submitted. If such archival tissue is not available for submission, then a 
re-biopsy is required.
The translocation t(11;14)(q13:q32) by FISH is optional and is not sufficient as sole proof for 
diagnosis. Evidence of the translocation t(11;14)(q13:q32) by FISH can be submitted using the 
original slide or the corresponding confirming photographies. If available, it is also 
recommended to send, for central pathology review, slides containing immunostaining for CD3, 
CD5, CD 10, CD20, CD23, BCL2, Ki-67.
Furthermore, it is highly recommended to perform an unilateral bone marrow biopsy at 
screening, and to send the tumor block to Central Pathology for review at the latest 8 weeks after 
randomization.
 
The central pathologist will also review any pathology specimens obtained as part of response 
assessment, including assessment of bone marrow biopsy required for response assessment of 
CR/CRu.  
For further details, please refer to central pathology manual.
&(/*
central pat
central pat
ssessment,
ssessment,
CR/CRu
CR/CRu
f
*(1(35235,(7$5<,1)250$7,21
retrospectiv
trospecti
nclude a bi
clude a bi
yclin D1 by
yclin D1 
yclin D1 ov
clin D1 ov
hemistry
mistry wi
w
y
slides fro
slides fr
des support
es suppo
1 staining),
1 staining)
ut at the lat
ut at the 
nal paraffin
nal paraffi
e tum
tumor bl
or bl
archival t
rchival tisis
by
by FISH i
FISH
y
s
cata ioion t(11
n t(1
ding confirm
ng confirm
entral patho
entral pat
23, BCL2
23, BCL
K
ghly
hly reco
recomm
m
send the tum
end the tum
*(
/*

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
59
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
8.5.
Independent Review Committee (IRC)
Diagnostic imaging results (CT with contrast /MRI with contrast) will be reviewed locally and 
also sent to IRC for central review. The IRC is composed of two external radiologists with an 
additional radiologist (adjudicator), in the event of a tie, and a hemato/-oncologist. The IRC will 
perform a blinded, independent assessment of radiological response (including assessment of SD 
and PD), review the tumor response data and the dates of disease progression for each patient. 
All these data reviewed by the IRC will be used in the primary analysis and these assessments 
will be included in the Clinical Study Report. 
For further details please refer to Central Radiology Manual.
&(/*(1(35235,(7$5<,1)250$7,21

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
60
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
9.
STUDY POPULATION
9.1.
Patient Inclusion Criteria
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Patients with histologically proven mantle cell non-Hodgkin’s lymphoma [MCL] 
{including overexpression of cyclin D1 by immunohistochemistry}. In patients whose 
tumors are negative for the cyclin D1 overexpression or translocation, evidence of 
overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable 
1. Patients who are refractory to their regimen or have relapsed once, twice or three times 
and who have documented progressive disease. (Refractory to prior chemotherapy 
regimens is defined as not having reached a CR or PR to prior treatment)
2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
3. Must be #18 years of age at the time of signing the informed consent form
4. Must have had at least one prior combination chemotherapy regimen with an alkylating 
agent, and comprising either an anthracycline and/or cytarabine and/or fludarabine (with 
or without rituximab)
5. Prior stem cell transplant is allowed
6. Must be ineligible for intensive chemotherapy and/or transplant at time of inclusion in the 
study
7. Must have measurable disease on cross sectional imaging by CT or MRI, if CT is 
contraindicated that is at least 2 cm in the longest diameter and measurable in two 
perpendicular dimensions
8. Must be able to adhere to the study visit schedule and other protocol requirements
9. Life expectancy of greater than 3 months
10. Females of childbearing potential (FCBP)† must:
!
Have two negative medically supervised pregnancy tests prior to starting of study 
therapy. She must agree to ongoing pregnancy testing during the course of the study, 
and after end of study therapy (see specifics in Appendix 21.8). This applies even if 
the patient practices complete and continued sexual abstinence
!
Either commit to continued abstinence from heterosexual intercourse (which must be 
reviewed on a monthly basis) or agree to use, and be able to comply with, highly 
effective contraception without interruption, at least 28 days prior to starting study 
drug, during the study therapy (including dose interruptions), and for at least 28 days 
after discontinuation of study therapy (see specifics in Appendix 21.8).
†A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) 
has not been naturally postmenopausal (i.e., amenorrhea following cancer therapy does not rule out childbearing 
potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive 
months)
&(/*(1(35235,(7$5<,1)250$7,21
ee times
ee times
herapy
erapy
)
core of 0, 1
core of 0, 
nsent form
nsent for
regimen w
regimen
arabine and
rabine and
y and
and/or
or
d
tran
t
s sectional i
s sectional 
in the lo
n the long
ng
e study
study visi
vi
y
i
er than 3 m
er than 3 m
ring potenti
ring poten
egat
gative med
me
he m
he must ag
ust a
m
ter end of s
ter end of s
patient
patient pra
p
Ei
Either com
ther com
i
reviewe
eview
effec
effe
d

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
61
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
11. Male patients must:
!
Agree to use a condom during sexual contact with a FCBP, even if they have had a 
vasectomy, throughout study drug therapy, during any dose interruption and after 
cessation of study therapy (see specifics in Appendix 21.8).
!
Agree to not donate semen or sperm during study drug therapy and for at least 28 
days after end of study drug therapy (see specifics in Appendix 21.8).
12. All patients must:
!
Have an understanding that the study drug could have a potential teratogenic risk
!
Agree to abstain from donating blood while taking study drug therapy and for at least 
28 days after end of study drug therapy (see specifics in Appendix 21.8).
!
Agree not to share study medication with another person
!
Agree to be counseled about pregnancy precautions and risks of fetal exposure.  See
Appendix 21.8)
9.2.
Patient Exclusion Criteria
1. Diagnosis of lymphoma other than mantle cell lymphoma
2. Prior history of malignancies, other than mantle cell lymphoma, unless the patient has 
been free of the disease for ≥ 5 years. Exceptions include the following:
!
Basal cell carcinoma of the skin
!
Squamous cell carcinoma of the skin
!
Carcinoma in situ of the cervix
!
Carcinoma in situ of the breast
!
Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
3. Transformed lymphoma
4. Prior use of lenalidomide
5. Prior radiotherapy within 4 weeks prior to randomization.
6. Patients who are candidates for autologous or allogeneic transplantation at the time of 
inclusion into the study.
7. Prior allogeneic transplantation with persistent donor hematopoiesis
8. Active CNS lymphoma with the exception of those patients whose CNS lymphoma has 
been treated with chemotherapy, radiotherapy or surgery, have remained asymptomatic 
for 90 days (3 months) and demonstrate no CNS lymphoma as shown by lumbar 
puncture, CT/brain MRI are eligible.  Patients with a history of CNS involvement or CNS 
symptoms will be required to have negative CSF cytology examination and a head CT 
during the screening period (known and active CNS or leptomeningeal involvement)
&(/*(1(35235,(7$5<,1)250$7,21
sk
for r atat lea
eastst
f fetal expo
fetal expo
ma
ma
ell lympho
ell lympho
ons include 
ns include
in
east
east
l finding of
 finding o
ma
ma
do
d mide
mide
erapy
rapy wi
wi
y
thi
th
i
who are c
who are can
a
on int
into the
o th
ior all
r allogen
ogen
Act
Active C
ive 
been t
been t
fofo

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
62
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
9. Known seropositive for or active viral infection with human immunodeficiency virus 
(HIV)
10. Known seropositive for or active viral infection with hepatitis B virus: 
∀
HBsAg positive.
∀
HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral 
DNA.
∀
Patients who are HBsAg negative and viral DNA negative are eligible.
∀
Patients who had hepatitis B but have received an antiviral treatment and show no 
detectable viral DNA for 6 months are eligible.
∀
Patients who are seropositive because of hepatitis B virus vaccine are eligible.
11. Known seropositive for or active viral infection with hepatitis C virus (HCV)
∀
Patients who had hepatitis C but have received an antiviral treatment and show no 
detectable viral RNA for 6 months are eligible.
12. Patients who are not willing to take DVT prophylaxis, if they are at risk (see definition in
Section 10.1.6)
13. Patients should not be receiving corticosteroids 7 days prior to randomization, except for 
prednisone ≤ 10 mg/day or equivalent for purposes other than treating MCL
14. Pregnant or lactating females
15. Any of the additional laboratory abnormalities. 
!
Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L)
!
Platelet count < 60,000/mm3(60 x 109/L)
!
Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT)
> 3.0 x upper limit of normal (ULN), except in patients with documented liver 
involvement by lymphoma
!
Serum total bilirubin > 1.5 x ULN, except in case of Gilbert’s Syndrome and 
documented liver involvement by lymphoma.
!
Calculated creatinine clearance (Cockcroft – Gault formula) of <30 mL/min
16. Any serious medical condition, laboratory abnormality, or psychiatric illness that would 
prevent the patient from signing the informed consent form
17. Participation in another clinical trial during the screening/baseline phase and treatment 
phase of the study
18. Any use of experimental drug during 4 weeks prior to randomization 
&(/*(1(35235,(7$5<,1)250$7,21
how no 
how no 
are eligible
re eligible
(HCV)
(HCV)
treatm
treatment t
ey are at ri
ey are at r
ays pri
ys prior to 
or to 
es other tha
s other t
alitities.
ies.
C) < 1,500 c
) < 1,500 c
(60
(60 x 10
x 109/L
minase (AST
nase (AS
norm
ormal (U
al (U
mphom
mphoma
ilirubin > 1
lirubin 
d liver invo
d liver invo
ated creatin
ated creatin
erious med
ious med
vent the
ent the pa
pa
Parti
Pa
cicipati
pati
i
phase o
phase o
18.
18. An
An

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
63
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
10.
DESCRIPTION OF TREATMENT 
10.1.
Treatment Assignments
The duration of a treatment cycle will be 28 days. The first dose of lenalidomide in cycle 1 
defines day 1 of the treatment cycle, and each cycle thereafter will begin 29 days later.
The 28-day cycle length should be maintained throughout the entire treatment phase regardless 
of the dose interruptions and/or dose reductions.
10.1.1.
Arm A
All patients who qualify for enrollment into the study will be randomized 2:1 to receive 
lenalidomide monotherapy (Arm A) or the investigator’s choice (Arm B). 
Patients in Arm A, 
!
Patients, who have a creatinine clearance ≥ 60 mL/min, will receive oral lenalidomide 
that is initiated on Day [D] 1 of Cycle 1 at a dose of 25 mg p.o. once daily for 21 days
(D1 – D21) in each 28 day cycle. A minimum 7 day rest period is mandatory before 
starting each new treatment cycle regardless of allowed ± visit windows.
!
Patients who have moderate renal insufficiency [creatinine clearance ≥ 30 mL/min but 
< 60 mL/min] will receive a lower starting dose of lenalidomide of 10 mg once daily
for 21 days (D1 – D21) in Cycle 1 and Cycle 2. A minimum 7 day rest period is 
mandatory before starting each new treatment cycle regardless of allowed ± visit 
windows. After Cycle 2, if the patient remains free of Grade 3 or Grade 4 toxicity, the 
dose will be increased to 15 mg once daily for 21 days (D1 – D21) in each 28 day 
cycle. 
Treatment is continued until disease progression or unacceptable toxicity. 
10.1.2.
Arm B
Patients in Arm B will receive investigator’s choice single agent reference therapy. This 
includes:
Chlorambucil tablets 2 mg;
Rituximab 500 mg vials;
Cytarabine Injection Solution 100 mg/ml;
Gemcitabine 1g vial;
Fludarabine 10 mg film-coated tablets;
Fludarabine 25mg/ml Concentrate for Solution for Injection or Infusion
Please refer to the prescribing information provided by Celgene on all of the above
For dosing of the investigators choice single agents, please refer to Table 6 based on published 
data and expert opinions.
&(/*(1(35235,(7$5<,1)250$7,21
ve
ceive oral
ceive oral ll
p.o.
p.o. once d
once 
period is m
eriod is m
d ± visit w
it w
creatinine c
creatinine 
e of lenalid
e of lenalid
e 2.
e 2. A min
A min
ment cy
ent cycle
c
remains fr
remains fr
ce daily for
ce daily for
ogressi
gress on o
on
e invest
investigat
iga
ets 2 mg
ts 2 m ;
mg vials
g vials
m
;
e Inject
Injectioion n
tabine 1g
abine 1g
udarabine 
udarabine 
Fludarab
Fludarab
Plea
e

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
64
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Investigators should refer to the approved Summary of Product Characteristics (SPC), provided 
by Celgene, for the investigator’s choice therapy for complete prescribing information including 
administration, warnings, precautions, contraindications, and adverse reactions and follow 
institutional procedures for the administration of the agents, where applicable. Paper prints will 
be provided in the Investigator's and Pharmacy binders.
The investigator’s choice treatment will be provided by Celgene.
Table 6:
Overview of dosage of Investigator's choice drugs 
Investigator’s choice*
mg/m2
Days
q days
max # cycles
Chlorambucil p.o. 
(Rai, 2000; Ardeshna, 
2003)
40 (total monthly 
dose)
Split over 3-10
days
28
until PD or 
toxicity
Rituximab i.v. 
(Ghielmini, 2000)
375
1, 8, 15, 22
56#
until PD or 
toxicity
Cytarabine i.v. 
(Kantarjian, 1983;   
UK SPC)
1 -2 g/m2 once or 
twice per day
1, 2
28
6
Gemcitabine i.v. 
(Dumontet, 2001)
1000
1, 8, 15
28
6
Fludarabine i.v. 
(Decaudin, 1998;
Zinzani, 2000)
25
1-5
28
6
Fludarabine p.o.
(Tobinai, 2006)
40
1-5
28
6
q days, repeated; y, years; i.v., intravenous; p.o., oral; 
* Refer to the approved Summary of Product Characteristics (SPC), provided by Celgene for the investigator’s 
choice therapy for complete prescribing information including administration, warnings, precautions, 
contraindications, and adverse reactions and follow institutional procedures for the administration of the agents, 
where applicable.
# Rituximab (single agent) is to be repeated every 56 days after Day 56 (given only on day 1 of every 56 days 
cycle). For the prevention of cytokine release syndrome associated with the treatment of Rituximab ≤125mg of 
methylprednisolone or equivalent are accepted on C1D1.
Patients in Arm B need to follow the scheduled visits as displayed in Table 2. For some drugs, 
additional visits may be needed.
10.1.3.
Dose Modification or Interruption for Lenalidomide - Arm A
a) Dose modification 
Patients will be evaluated for adverse events at each visit with the NCI CTCAE v3.0 used as a 
guide for the grading of severity.  The dose of lenalidomide for each patient will be interrupted 
and modified following toxicity as described below.
Refer to Table 7 for instructions on dose modifications and Table 8 and Table 9 for dose 
reduction instructions for lenalidomide.
&(/*(1(35235,(7$5<,1)250$7,21
cles
es
7
$7
or 
o
ity
ity
0$
until PD
until PD
toxici
toxici
25
)2
6
1)
28
28
5<
$5
7$
1-5
-5
,(
35
.o., oral;
.o., oral;
uct Character
t Characte
ng informatio
ng informati
ctions and fol
tions and f
be repeated
repe
of cytokine r
of cytokine
equivalent ar
quivalent a
B need to fo
B need to f
ts may
s may b
y e n
e
Dose M
Dose M
ose modifi
ose modif
Pati
Patients wi
ents wi
gui
guide f
de fof
d m

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
65
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 7:
Dose Modification for Lenalidomide
NCI CTCAE
Toxicity Grade
Action Required
Sustained(≥7 days) Grade 3 
neutropenia or ≥ Grade 3 associated 
with fever (temperature ≥ 38.5º C) or 
Grade 4 neutropenia
!
Hold (interrupt dose)
!
Follow CBC at least every seven days
!
If neutropenia has resolved to ≤Grade 2 restart at next 
lower dose level
!
Use of growth factors (G-CSF, GM-CSF) is permitted at 
the discretion of the investigator
Thrombocytopenia ≥Grade 3 (platelet 
count < 50,000 cells/mm³ [50x109/L])
!
Hold (interrupt dose)
!
Follow CBC weekly at least every seven days
!
If thrombocytopenia resolves to ≥ 60,000 cells/mm³ (60 x 
109/L) restart at next lower dose level.
Desquamating (blistering) Rash
≥ Grade 3 or
non-desquamating 
Rash Grade 4
!
Discontinue lenalidomide study drug
Allergic reaction or hypersensitivity
Grade 2
Grade 3-4
!
Hold (interrupt dose).  Follow at least every seven days
!
When the toxicity resolves to ≤ Grade 1 restart at next 
lower dose level
!
Discontinue lenalidomide study drug
Constipation
Grade 1-2
≥ Grade 3
!
Initiate bowel regimen and maintain dose level
!
When the toxicity resolves to ≤ Grade 2 restart at next 
lower dose level
Venous thrombosis/embolism
≥ Grade 3
!
Hold (interrupt) dose and start anticoagulation; restart at 
investigator’s discretion (maintain dose level)
Newly developed ≥ Grade 3 peripheral 
neuropathy (this applies only to those 
toxicities which begin or worsen
while on study)
!
Hold (interrupt) dose
!
When the toxicity resolves to ≤ Grade 2 restart at next 
lower dose level
&(/
ewly develo
ewly develo
neuropathy
neuropathy
oxicitie
oxiciti
le
(/*(1(35235,(7$5<,1)250$7,21
mitted at 
ed at 
$7
even days
even days
≥ 60,000 
≥ 60,000
er dose leve
dose leve
50
mide study d
mide stud
< ,
(interrupt do
(interrupt do
When
When the
the tox
tox
e
lower dos
lower dos
!
D
(7$
52
5
mbosis/em
mbosis/em
3
*(
(/

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
66
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 7:
Dose Modification for Lenalidomide (Continued)
NCI CTCAE
Toxicity Grade
Action Required
AST or ALT > 3 x ULN
Hold lenalidomide dosing; re-
test at least weekly until AST 
or ALT < 2.5 x ULN or return 
to baseline 
∀
Resume the same dose of 
lenalidomide if the event is 
considered NOT related to 
study drug treatment
∀
Restart lenalidomide 
treatment at next lower 
dose level if the event is 
considered as related to 
drug treatment
Bilirubin > 3 x ULN*
Hold lenalidomide dosing; re-
test at least weekly until 
bilirubin < 1.5 x ULN 
∀
Resume the same dose of 
lenalidomide if the event 
is considered NOT related 
to study drug treatment
∀
Restart lenalidomide 
treatment at next lower 
dose level if the event is 
considered as related to 
drug treatment
Tumor Flare
Grade 3 or 4
!
Interrupt lenalidomide therapy and initiate therapy 
with corticosteroids, NSAIDs and/or narcotics
!
Resume lenalidomide (decrease one dose level) 
when symptoms resolve to & Grade 1
TLS
laboratory TLS and Grade 1 TLS
!
Same dose of lenalidomide may be continued 
without interruption or dose reduction at the 
investigator’s discretion.
!
Dose escalation to the next consecutive dose level 
is permitted when laboratory TLS is resolved and 
Grade 1 TLS is resolved to Grade 0.
TLS ≥ Grade 2
!
Interrupt lenalidomide therapy.
!
May resume lenalidomide when the TLS resolves 
to < Grade 1 (decrease one dose level)
!
If lenalidomide is resumed prior to the start of the 
subsequent cycle, a chemistry test should be
performed every other day for the first week 
following initiation of lenalidomide.
&(/*
Grade 2
Grade 2
/*(1(35235,(
!
Inte
Inte
w
5,(7$5<,1)250$7,21
lower 
wer 
he event is
he event i
d as related t
as related 
eatment
atment
$7
Resume the
Resume
lenalidom
lenalido
is con
is c
to 
to
∀
)2
5<
5,(
52
1 TLS
1 TLS
5
/*

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
67
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 7:
Dose Modification for Lenalidomide (Continued)
NCI CTCAE
Toxicity Grade
Action Required
!
Re-escalation by one dose level at a time will be 
permitted after completion of one full cycle without 
laboratory TLS or ≥ Grade 1 TLS 
Any other lenalidomide-related non-
hematologic AE ≥ Grade 3 not 
requiring definitive treatment 
discontinuation
!
Hold (interrupt lenalidomide dose).  
!
When the AE resolves to ≤ Grade 2 restart at the 
same or at next lower dose level according to 
investigator’s discretion
* For patients with Gilberts Syndrome or liver involvement by lymphoma, dose reductions should 
be made in consultation with the Celgene medical monitor
If a patient experiences an AE that requires a dose interruption, the patient can not be re-started 
on study medication until the AE has resolved or reached acceptable grade described in Table 7.  
Once the AE has resolved, the patient may continue back on lenalidomide (at the dose level 
required in Table 7, and refer to Table 8 and Table 9 for the actual dose) for the remainder of the 
cycle. Doses that were missed, because of toxicity or any other reason, will not be rescheduled. 
If a cycle is delayed due to an AE the patient can re-start lenalidomide within a next cycle once a
7-day rest period has occurred and the requirements mentioned below have been met. 
The study assessments should remain in line with dosing days (actual number of days that 
lenalidomide has been taken) but the tumor assessments will be determined from Cycle 1 Day 1 
following counting calendar days and do not follow the dosing cycles.
The next cycle of treatment may begin on the scheduled Day 1 if:
!
The minimum 7 day rest period has elapsed following the last dose of study drug in 
the prior cycle (the rest period is mandatory regardless of allowed ± visit windows)
!
The ANC is ≥1,000 cells/mm³ (1.0 X 109/L);
!
The platelet count is ≥ 60,000 cells/mm³ (60 X 109/L);
!
Lenalidomide related allergic reaction or hypersensitivity not requiring 
discontinuation has resolved to ≤ Grade 1 severity;
!
Any other lenalidomide-related AE not requiring definitive treatment discontinuation 
has resolved to ≤Grade 2 severity.
If these conditions are not met on Day 1 of a new cycle, the patient will be evaluated at least 
once every seven days and a new cycle of lenalidomide will not be initiated until the toxicity has 
resolved as described above.
If a new cycle is delayed for more than 28 days, the 
 Medical Monitor must be notified
and treatment can be resumed according to the treating physicians’ and 
Medical 
&(/*(1(35235,(7$5<,1)250$7,21
7
t at t the
the
ding to
ding to
7
25
$7
ose reductio
ose reduc
atient can n
tient can n
le grade de
e grade d
alido
alidomide 
actual dose
actual dos
other reaso
other reaso
art lenalido
art lenalid
ts s me
m ntntioione
ne
ith dosing
dosing
assessmen
ssessmen
not
not fo
follo
ll w
35
in on the sc
in on the
rest peri
rest period
od
e rest perio
e rest perio
1,000 cell
1,000 c
let count is
et count i
ido
idomid
mide re
e r
continuat
ontinuati
Any othe
Any othe
has re
as re
these cond
hese cond
once ever
once ever
esolve
esolve

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
68
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Monitors’ clinical judgment. The Medical monitor may consult Celgene Clinical Research 
Physician for clinical judgment if appropriate.
If lenalidomide dosing was halted during the previous cycle and was restarted with a one-level 
dose reduction without requiring an interruption for the remainder of the cycle, then that reduced 
dose level will be initiated on Day 1 of the new cycle. 
There will be no more than one dose reduction from one cycle to the next.
Once a dose reduction occurred, no re-escalation is permitted.
b) Dose reduction
The daily dose of lenalidomide may be reduced successively by one level from the starting dose 
of 25 mg p.o. once daily for 21 days (D1 – D21) in each 28 day cycle for patients with a 
creatinine clearance ≥ 60 mL/min (refer to dose reduction steps in Table 8) in case of severe 
toxicity.  
Creatinine clearance (use Cockcroft – Gault formula) should be determined utilizing actual body 
weight or ideal body weight, which ever is less. For patients who have moderate renal 
insufficiency [creatinine clearance ≥ 30 mL/min but < 60 mL/min], refer to dose reduction steps 
in Table 9.
Table 8:
Dose reduction steps for Adverse Events related to Lenalidomide for patients 
initiating treatment at 25 mg daily on Days 1-21, every 28 days 
Starting Dose
25 mg daily on Days 1-21, every 28 days
Level –1 Dose
20 mg daily on Days 1-21, every 28 days
Level –2 Dose
15 mg daily on Days 1-21, every 28 days
Level –3 Dose
10 mg daily on Days 1-21, every 28 days
Level –4 Dose
5 mg daily on Days 1-21, every 28 days
Level –5 Dose*
5 mg every other day between Days 1-21, every 28 
days
*Once a patient’s dose has been reduced, no dose re-escalation is permitted.  Patients who cannot tolerate 
dose level 5 have to be discontinued from the Treatment Phase of the study.
Table 9:
Dose reduction steps for Adverse Events related to Lenalidomide for patients 
initiating treatment at 10 mg daily on Days 1-21, every 28 days
Starting Dose
10 mg daily on Days 1-21, every 28 days
Level –1 Dose*
5 mg daily on Days 1-21, every 28 days
Level –2 Dose*
5 mg every other day between Days 1-21, every 28 
days
*Once a patient’s dose has been reduced, no dose re-escalation is permitted.  Patients who cannot tolerate 
dose level -2 are to be discontinued from the Treatment Phase of the study.
Level
Level –2
–2
(/*(1(35235,(7$5<,1)250$7,21
ting dose
ting dose
th a 
h a 
e of severe
of severe
ed utilizing 
d utilizing 
moderate r
moderate
refer to dos
er to dos
f
lated to Le
lated to L
ays 1
ays 1-21, ev
21, e
25 m
25 mg dai
g dai
$5
20 mg daily
20 mg dai
(7$
,
15 mg 
15 mg
,(
5,
10
10
5,
5,
5,
5,
35
23
35
reduced, no 
educed, no
ontinued from
ntinued f
Dose reduct
Dose reduc
initiating
initiating
St
S
*(
–1
–1 Dose
Dose*
/*
Do
Do
(/
&
nce

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
69
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
10.1.4.
Dose Modification or Interruption for Investigator’s choice - Arm B
Patients will be evaluated for adverse events at each visit with the NCI CTCAE v3.0 used as a 
guide for the grading of severity.  The dose of investigator’s choice for each patient will be 
interrupted and modified according to the clinical practice of the investigators institution, where 
applicable and in line with the approved prescribing information provided by Celgene. Doses 
that were missed because of toxicity or any other reason will not be made up.  Patients should 
continue with the next cycle when they are able.
10.1.5.
Tumor Lysis and Tumor Flare - Lenalidomide
In a preliminary report of a study conducted with lenalidomide in relapsed/refractory chronic 
lymphocytic leukemia (CLL), some patients experienced tumor lysis syndrome, tumor flare 
reaction and occasionally cytopenias (neutropenia and thrombocytopenia) during the first week 
of Cycle 1 (Chanan-Khan, 2006; Moutouh-de Parseval, 2007; Andritsos, 2008; Eve, 2010). In 
some CLL patients, tumor flare and tumor lysis have been life-threatening and fatal. Among the 
NHL patients treated with lenalidomide in Celgene sponsored clinical trials in NHL patients 
(total number of NHL patients in database of approximately 250), four patients with tumor flares 
and one patient with tumor lysis have been reported.  In addition, one patient with tumor flare 
and one patient with tumor lysis have been reported outside of clinical trials.  Thus, in this study, 
patients should be monitored for tumor flare and tumor lysis.  
Tumor lysis syndrome (TLS) can be defined as a constellation of metabolic abnormalities 
resulting from spontaneous or treatment related tumor necrosis or fulminant apoptosis. The 
metabolic abnormalities include: hyperkalemia, hyperuricemia and hyperphosphatemia with 
secondary hypocalcaemia. 
The onset of TLS is rapid, usually within 24 to 48 hours after the first dose but can also occur 
after the first week of treatment.  The presence of known risk factors like bulky disease, 
moderate renal insufficiency, high ALC and high uric acid levels (> 8 mg/dL) prior to therapy 
increases the likelihood of TLS.  Early identification of patients at risk and the prevention of 
TLS development with the initiation of preventive measures as well as the careful monitoring for 
early signs of laboratory TLS and the prompt initiation of supportive care are critical to prevent 
potentially life-threatening metabolic derangements (Cairo, 2004).  
Patients in the lenalidomide arm in this study should receive tumor lysis prophylaxis (allopurinol 
or equivalent) and be well hydrated (orally) during the first 7 days of lenalidomide 
administration in the first cycle or as clinically indicated. Hydration levels should be adjusted 
according to age and clinical status. To monitor for tumor lysis syndrome and cytopenia(s), the 
patients will have a (CBC) and chemistry drawn on Days 1, 2, 4, 8 and 15 of the first cycle and 
additionally as clinically indicated. TLS will be assessed by Cairo-Bishop Grading system (see 
Appendix 21.6).
If a patient develops laboratory TLS (defined by the presence of two or more serum value 
abnormalities of uric acid, potassium, phosphorous or calcium) or ≥ Grade 1 TLS (defined by the 
presence of laboratory TLS and one or more of the following criteria: creatinine ≥ 1.5 x ULN, 
arrhythmia or seizures), appropriate medical management should be initiated according to the 
local standard of care in each institution with vigorous IV hydration (rasburicase treatment is 
considered appropriate if it is approved by the local Health Authority).
&(/*(1(35235,(7$5<,1)250$7,21
onic
nic
or flare
r flare
he first
he first wee
we
Ev
Eve, 2010
e, 201 )
d fatal
d fat . Am
A
als in NHL 
ls in NHL 
patients w
patients w
ne pati
patient w
ent w
inical trials
ical trial
tion of me
n of me
necrosis or 
necrosis or
eruricemia
eruricemi
to 48 hours
o 48 hours
ence of kn
ence of kn
C and high 
and high
rly ident
ly identific
i
ion of prev
n of pre
and the pro
and the pr
metabo
metabolic d
lic
mide arm
mide arm in
e well hydr
well hyd
the first cy
the first cy
ge and clin
e and cli
h
l ave a
ave a (C
ally as clini
as clin
y
ndix
ndix 21.6
21.6)
a a 
&
patient
patient d
abnorm
bnormalal
es
esen
en

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
70
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Tumor flare reaction (TFR) is defined as a sudden and tender increase in the size of the disease 
bearing sites, including the lymph nodes, spleen and or the liver often accompanied by low-grade 
fever, non-pruritic diffuse rash and in some cases increase in the peripheral blood lymphocyte 
counts. The onset of tumor flare may be as early as within a couple of hours after the first dose 
and has a median duration of 14 days. This usually occurs only during the first cycle of 
treatment. Tumor flare will be recorded as an AE (graded using the NCI CTCAE criteria version
3) and not as progressive disease (PD) and will be treated symptomatically first with non-
steroidal anti-inflammatory agents (NSAIDs). Narcotics or prednisone may be used at the 
investigator’s discretion, to treat the tumor flare reaction.
10.1.6.
Thromboembolism - Lenalidomide
All patients treated with lenalidomide regardless of prior thromboembolic history will receive 
prophylactic aspirin [ASA] (70 – 100 mg) daily unless contraindicated.  If ASA is 
contraindicated, use of low molecular weight heparin or warfarin (or equivalent Vitamin K 
antagonist) to keep the International normalized ratio (INR) in the range of 2-3 may be 
considered.
The choice of prophylactic agent(s), and also the interruption or discontinuation of such 
prophylaxis if needed, should be based on the local standard of care and the investigator’s best 
judgement after careful consideration of the benefit versus the potential risk for the individual 
patient.
10.1.7.
Prior/Concomitant medications and other permitted concomitant therapies
Prior/Concomitant Medications
All medications (prescription, non-prescription and herbal), treatments and therapies taken from 
30 days prior to the start of study drug through the last dose of study drug, must be recorded on 
the appropriate page of the electronic Case Report Form (eCRF). For subjects included in the 
Extension Access Phase information will no longer be collected on the eCRF. The investigator 
should ensure concomitant medications continue to be recorded in the subjects’ medical records.
Other permitted concomitant therapies
Other therapies considered necessary for the patient’s well being may be administered at the 
discretion of the Investigator. 
Other recommended medications such as ASA, allopurinol, low molecular weight heparin, 
warfarin, analgesics, antihistamines, or other medications such as growth factors, and 
transfusions of red blood cells, platelets, or fresh frozen plasma given to assist in the 
management of complications associated with cancer or its therapy, will be provided by the 
investigative site, Celgene will not provide these medications. 
Growth factors (e.g. G-CSF, GM-CSF, erythropoietin, platelets growth factors etc.) are not to be 
administered prophylactically, but may be prescribed by the investigator for rescue from severe 
hematologic events, if it is thought to be appropriate. They should be used in accordance with the 
American Society of Clinical Oncology’s (ASCO) and European Society for Medical Oncology
(ESMO) guidelines, and recorded on concomitant medications CRF page. 
&(/*(1(35235,(7$5<,1)250$7,21
ill receive
ill receive
s s 
nt Vitamin 
nt Vitamin
f 2-3 
-3 ma
may y b
contntinuat
inua ioi
are and the
e and th
potential r
potentia
er
er permitt
permitt
n and herb
n and herb
ough the las
ough the la
ase Report
ase Repor
will no lon
will no l
atatioions cont
ns con
nt therapi
nt therapi
ed necessary
d neces
tigator.
gator
ed medicat
d medicat
esics, ant
esics, antih
of red bloo
of red blo
ment of com
nt of com
gat
gative site,
ive site,
rowth facto
owth facto
administer
dminister
hemato
emato

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
71
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
10.1.8.
Prohibited concomitant therapy
Concomitant use of other anti-cancer therapy while the patient is in the study is prohibited. 
Physiological doses of steroids (defined as ≤ 10 mg prednisone per day, or equivalent) are 
allowed during the study. Doses beyond 10 mg prednisone per day (or equivalent) are not 
allowed during the study or during the last 7 days of the screening period except for the 
treatment of tumor flare and for the prevention of cytokine release syndrome associated with the 
treatment of Rituximab on C1D1.
No investigational therapies or non-drug therapies shall be initiated while the patient is receiving 
lenalidomide.
Following the approval of Protocol Amendment #6, concomitant medications will no longer be 
collected and recorded in a specific CRF but should continue to be recorded in the subjects’
medical records.
10.2.
Discontinuation from Treatment
The following events are considered sufficient reasons for discontinuing a patient from study 
drug:
!
Adverse event(s) that, in the judgment of the Investigator, may cause severe or 
permanent harm or which rule out continuation of study drug.
!
Disease Progression, disease relapse
!
Patient partially withdraws consent (withdraws from treatment only).
!
Patient is lost to follow-up
!
Death
!
Protocol violation
The reason for discontinuation should be recorded in the CRF and in the patient’s medical 
records. Celgene is to be notified of all discontinuations from study drug.
Following the approval of the Protocol Amendment #6 reasons for discontinuation will no longer 
be recorded on a CRF, but they will be recorded in the subjects' medical records.
&(/*(1(35
e
35235,(7$5<,1)250$7,21
ing 
ng
onger be 
onger be 
ubject
ubjects’s’
g a pati
a patient 
en
gator, may
gator, may
f study
f stud drug
dru
y
draws from
draws fro
uld be recor
d be reco
d of all disc
d of all disc
Protocol 
Protoc
ut they
ut they will 
w
y

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
72
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
11.
STUDY DRUG MATERIALS AND MANAGEMENT
11.1.
Supplier(s)
Celgene Corporation will supply oral lenalidomide capsules.
Celgene Corporation will provide commercial supplies of investigator choice therapies (see 
Table 6) and these therapies will be labeled appropriately as investigational material for the
study. Celgene will not provide other recommended medications such as aspirin.
11.2.
Dosage Form
Lenalidomide will be supplied as 5 mg, 10 mg, 20 mg and 25 mg capsules for oral 
administration.
The investigators choice therapies will be supplied as described in Table 6.
Following the approval of Protocol Amendment #6, Celgene Corporation will supply 5 mg, 10 -
mg, 20 mg, and 25 mg strengths in countries where lenalidomide is only available under a 
clinical trial protocol. No more than a 21-day supply of study drug will be dispensed at a time.
11.3.
Dosage Regimen
11.3.1.
Lenalidomide
Lenalidomide will be supplied in bottles containing a 21 day supply.  No more than a 28-day 
supply of study drug will be dispensed at a time. Treatment is to be continued as tolerated (see
Section 10.1.3 Dose Moderation or Interruption) until disease progression or an unacceptable 
toxicity occurs.
Lenalidomide capsules should be swallowed whole, and should not be broken, chewed or 
opened.  
Patients should be instructed to take the study drug at the same time each day.
11.3.2.
Investigators Choice 
The investigators choice therapies will be provided as commercial supply and in the dosages as 
described in Table 6. 
11.4.
Drug Dispensing Requirements
In investigational studies, lenalidomide will be dispensed through a qualified healthcare 
professional (including but not limited to, nurses, pharmacists and physicians).  These healthcare 
professionals will be trained by Celgene in requirements specific to counseling of study patients.  
Once trained these healthcare staff will counsel study patients prior to study drug being 
dispensed to ensure that the study patient (FCBP & males) has complied with all requirements 
including use of birth control and pregnancy testing (FCBP) and that the study patient
understands the risks associated with lenalidomide.  This step will be documented by completing 
the Education and Counseling Guidance Document (Appendix 21.9), and no study drug will be 
dispensed until this step occurs.  Counseling includes verification with the study patient that 
&(/*(1(35235,(7$5<,1)250$7,21
will
will supply
supply
y available 
ailab
ill be dispe
ll be disp
21 day
21 day sup
sup
y
reatment is
reatment is
) unt
) until dise
il dis
wed who
wed whole
ake the stud
ke the stu
hoice
hoice
e therapies 
e therapie
ug Dispen
ug Dispen
ational stud
tional stud
onal (includ
l (inclu
ssio
ssionals wi
nals w
nce trained 
e trained
didispensed 
spensed 
ncludin
ncludi

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
73
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
required pregnancy testing was performed and results were negative. A Lenalidomide 
Information Sheet will be supplied as described in (Appendix 21.11).
11.5.
Special Handling Instructions
Health care providers should consider wearing gloves when directly handling Revlimid 
(lenalidomide) capsules followed by standard hand washing. All patients should not extensively 
handle or open lenalidomide capsules and should maintain storage of capsules in the packaging 
until ingestion.
11.6.
Treatment Compliance
Study personnel will review the dosing instructions with the patient prior to dispensing the study 
drug. The study drug bottle will be packaged with enough capsules for each 21-day treatment 
period. The patient will be instructed to return the study drug bottles, including any unused study 
drug to the site at the next visit. Patient compliance will be noted on the appropriate CRFs and 
source records based on a capsule count. To monitor treatment compliance, reconciliation of 
lenalidomide capsules will be done at each scheduled study visit. For subjects included in the 
Extension Access Phase drug accountability information will no longer be collected on eCRF. 
For subjects included in the Extended Access Phase, accountability of the study drug, including 
any drug lost or damaged, will be documented in the subjects’ Drug Accountability and Dosing 
Record Sheets.The investigator should ensure concomitant medications continue reported in the 
subjects’ medical record
11.7.
Packaging and Labeling
The lenalidomide study drug will be packaged in bottles and each bottle will contain 21 capsules.
The label for study drug supplied by Celgene will bear Celgene’s name and address, the protocol 
number, EudraCT number (as applicable), product name, dosage form and strength, medication 
identification/kit number, lot number, expiry date, dosing instructions, storage conditions, the 
quantity of study drug contained, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as needed or as applicable.
11.8.
Receipt and Storage
The Investigator, or designee, is responsible for taking an inventory of each shipment of study 
drug received, and comparing it with the accompanying study drug shipping order/packing slip. 
The Investigator, or designee, will verify the accuracy of the information on the form, sign and 
date it, retain a copy in the study file, and return a copy to Celgene.
At the study site, all investigational study drugs will be stored in a locked, safe area to prevent 
unauthorized access.
The study drug should be stored as directed on the respective package labels.
11.9.
Record of Administration
Following the approval of Protocol Amendment #6 for subjects included in the Extended Access 
Phase, accurate recording of study drug administration will be made in the subjects’ Drug 
&(/*(1(35235,(7$5<,1)250$7,21
ng the stud
ng the stud
ay treatmen
treatmen
y
 any unuse
any unu
ropriate CR
ropriate C
ce, reconcil
e, reco
subjects inc
subjects in
nger be col
nger be c
ity o
y of the s
e s
’ Drug Acc
’ Drug A
t medicatio
medicatio
d in bottles 
d in bottles
gene will be
ene will be
ble), produc
le), produc
er, expiry d
r, expiry 
, and requir
, and requi
atatioion ma
may y b
nd Storag
nd Stora
desi
esignee, 
gnee, 
nd comparin
nd compari
ator, or des
ator, or de
tain a copy
n a copy
e study
e study sisi
y
tete
i
authori
uthorized 
zed 
The study
The study

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
74
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Accountability and Dosing Record Sheets. This information will reviewed by the study monitor 
at their site monitoring visits.
11.10.
Accountability
An accurate accounting of the dispensing/return of study drug for each study patient will be 
maintained in source documents on an ongoing basis by a member of the study site staff.  
Additionally, if any study drug is lost or damaged or if the study patient misses a dose, this 
information should be documented in the study patient’s CRF and source documents.
Following the approval of Protocol Amendment #6 for subjects included in the Extended Access 
Phase, accountability of the study drug, including any drug lost or damaged, will be documented 
in the subjects’ Drug Accountability and Dosing Record Sheets.
11.11.
Handling and Disposal
Celgene will instruct the Investigator(s) on the return or destruction of unused study drug.
Following the approval of Protocol Amendment #6 for subjects included in the Extended Access 
Phase, accountability of the study drug, including any drug lost or damaged, will be documented 
in the subjects’ Drug Accountability and Dosing Record Sheets.
&(/*(1(35235,(7$5<,1)250$7,21
Access 
Access 
cumented 
umented
sed study d
sed study d
ed in the Ex
d in the E
amaged, w
aged, w

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
75
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
12.
ASSESSMENT OF EFFICACY
12.1.
Assessments
The following efficacy assessments will be done at baseline and at scheduled intervals 
throughout the duration of the study as outlined in “Schedule of Study Assessments”.
12.2.
Methods and Timing of Efficacy Assessments
Response and progression will be evaluated using the international criteria proposed by the 
Modified International Workshop Response Criteria (IWRC) (Cheson, 1999; as modified in 
Kane, 2007; Fisher, 2006) for target and non-target lesions. 
Date of documentation of disease progression
The date of documentation of disease progression will be the date of confirmation of disease 
progression whether on clinical or radiographic grounds.
CT scan/MRI
CT with contrast or alternatively MRI with contrast, if CT is contraindicated, is performed at 
baseline then every 56 days (±7 days) after Day 1, Cycle 1 for the first 6 months and then every 
90 days ± 15 days thereafter until documented progressive disease; or when clinically indicated. 
To ensure comparability, baseline and on-study methods for response assessment must be
performed using identical techniques. 
Any suspicion of progressive disease and eventually leading to additional investigations (e.g. 
colonoscopy) must be complemented by a re-staging procedure using CT scan (or MRI).
Bone Marrow Biopsy
Unilateral bone marrow biopsy during treatment is required only if patients has otherwise 
fulfilled the criteria for CR. The bone marrow procedure should be performed 28 days after the 
criteria for CR have otherwise been met. 
Physical Examination and ECOG
All patients will be examined for ECOG status (Appendix 21.3), and receive a physical exam 
including lymphadenopathy, hepatomegaly and splenomegaly as described in Table 2 and as 
clinically indicated.
Progression-free survival/Overall Survival
All patients will be followed for progression-free survival and for overall survival after 
progression every 90 days. Cause of death, disease progression and lymphoma therapies are to be 
recorded in the CRF and the patient’s medical record. Once patients have been discontinued 
from study drug, they will be followed for progression of disease (if applicable), lymphoma 
treatments, second primary malignancies and death. Patients will be followed until death or until 
either 70% of the patients have died or the median follow-up in responding patients is > 2 years 
or the median duration of response (overall response and CR/CRu) has been reached, or four
years from last patient randomized, whichever comes later, at which time the study will end for 
&(/*(1(35235,(7$5<,1)250$7,21
n n
on of disea
n of dis
aindicated,
aindicated
he first 6 m
he firs
isease
isease; or w
or
ds for respo
s for res
ally leadin
ally leadin
taging pro
aging pro
t
ng treatm
g treatmen
one marrow
one marr
been met.
een met.
nd ECOG
nd ECO
xamined fo
xamined f
denopathy
enopathy
ated.
ated.
n-free surv
free surv
ient
en s will b
will b
gression eve
ression ev
corded in
corded in
fro
rom stud
stud
eatm
eatm

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
76
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
subjects still on lenalidomide treatment in countries where lenalidomide is available post-trial in 
the commercial setting.
Following the approval of Protocol Amendment #6 an Extended Access Phase will be made 
available for subjects on study treatment in countries where lenalidomide is only available under 
a clinical trial protocol as post-trial access.
Subjects in the Extended Access Phase may remain on study until progressive disease or 
withdrawal for other reasons. Only serious adverse events (SAEs) including second primary 
malignancies (SPMs), and drug accountability record information will be collected and reported 
for these subjects. Follow-up survival data will no longer be collected by Celgene for these 
subjects.
Patients who withdraw consent for treatment will continue to be followed for safety, efficacy 
(disease progression), second primary malignancies and for survival. Patients in the follow-up 
phase who withdraw consent for efficacy (disease progression) follow-up will continue to be 
followed for second primary malignancies and for survival. A full consent withdrawal must be 
documented to disallow follow up for second primary malignancies and for survival.
&(/*(1(35235,(7$5<,1)250$7,21
ted d
y, efficacy
efficacy
he fo
he follo
llow
l continue t
continue 
withdrawa
withdrawa
for r surviva
surv

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
77
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
13.
ASSESSMENT OF SAFETY
13.1.
Assessments
!
AEs/SAEs severity is graded using NCI CTCAE Version 3.0 (see Appendix 21.1)
!
ECOG Performance Status
!
Vital signs: Blood pressure, pulse, weight and height (screening only).
!
Clinical laboratory evaluations: 
i.
Hematology Labs: Red blood cell (RBC) count, hemoglobin, hematocrit, 
MCV, white blood cell (WBC) count with differential, absolute neutrophil 
count (ANC), absolute lymphocyte count (ALC), and platelet count.
ii.
Chemistry Labs: Sodium, potassium, calcium, phosphorus, blood urea 
nitrogen (BUN), creatinine, glucose, albumin, total protein, alkaline 
phosphatase, total bilirubin, aspartate transaminase (AST/SGOT), alanine 
transaminase (ALT/SGPT), lactate dehydrogenase (LDH) and uric acid.
!
Serum/urine beta-human chorionic gonadotropin (β-hCG) (FCBP only)
!
Concomitant medications 
!
Hospitalizations   
!
Second primary malignancies will be monitored as events of interest and must be
reported as serious adverse events regardless of the treatment arm the subject is in 
(see Section 21.1.9).  This includes any second primary malignancy, regardless of 
causal relationship to study drug (lenalidomide or Investigator Choice arm drugs), 
occurring at any time for the duration of the study, from the time of signing the ICD 
through follow-up for overall survival. The Follow-Up Phase involves patient contact 
every 90 days (± 15 days) until patient death or until either 70% of the patients have 
died, or the median follow-up in responding patients is > 2 years, or the median 
duration of response (overall response and CR/CRu) has been reached, or four years 
from last patient randomized, whichever comes later, at which time the follow-up 
study phase will be closed.
!
12- lead ECG
!
Assessment of Lymphoma-related Symptoms 
!
Calculated creatinine clearance (Cockcroft-Gault formula)
!
Tumor Flare/Lysis Assessments (only for patients in Arm A and patients in cross 
over)
!
FCBP should be monitored during the course of the study and after the end of study 
therapy to (only for patients in Arm A and patients in cross over):
∀
Ensure that pregnancy tests are performed during the course of the study and after 
end of study therapy and are negative (See specifics as described in 
Appendix 21.8).
&(/*(1(35235,(7$5<,1)250$7,21
crit,
rit,
utrophil
trophil
ount.
ount.
blblood urea
ood ure
ein, alkaline
in, alkalin
AST/SGOT
ST/SG
(LDH) and
(LDH) an
CG) (FCBP
G) (FCBP
nitored as e
nitored a
ardless of th
rdless of 
any second
ny secon
(l(lenalido
enalidom
duration of 
duration of 
all survival
all survival
s) unt
 until pat
il pa
ollo
llow-
w-up in
up in
se (overall 
se (overall
nt randomiz
randomiz
will
will be clcl
l
os
o
ECG
CG
essment of
essment 
Calculated
Calculated
!
Tum
umo
ov
ov
!

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
78
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
∀
Ensure the study patient continues to practice abstinence or remains on adequate 
contraception (See specifics as described in Appendix 21.8).
∀
If a FCBP becomes pregnant, treatment should be stopped and the study patient
referred to the appropriate physician.
!
Male study patients should be monitored during the course of the study and after the 
end of study therapy to:
∀
Ensure they continue to use a condom during sexual contact with a FCBP
∀
If a female partner of a male study patient becomes pregnant she should be 
referred to the appropriate physician.
13.2.
Methods and Timing of Safety Assessments
Serial measurements of safety will be performed at baseline and at scheduled intervals 
throughout the duration of the study as outlined in “Schedule of Study Assessments (see
Table 2)” as well as for patients in the investigators choice Arm B who are crossing over to 
lenalidomide therapy (see Table 3).  All scheduled visits will have a ± 3 day window unless 
otherwise stated. The site’s local laboratory will perform laboratory testing.  
13.3.
Recording and Reporting of Adverse Events
The recording and reporting of adverse events is described in Appendix 21.1.
For Local Drug Safety Affiliate Office contact information, please refer to the Serious Adverse 
Event Report Form Completion Guidelines.
Extended Access Phase
Following the approval of Protocol Amendment #6, only serious adverse event reports will 
continue to be sent by the investigator to Celgene Safety. The SAE must be reported immediately 
(i.e., within 24 hours of the Investigators’ knowledge of the event) to Celgene Drug Safety by 
facsimile or e-mail.  An initial written report (prepared by the Investigator(s) using the SAE 
Report Form provided by Celgene) is to be faxed or e-mailed to Celgene Drug Safety. The 
immediate reporting process and timelines apply also to reporting second primary malignancies 
(see Appendix 21.1.2).
Non-serious adverse events will no longer be collected on a CRF by Celgene, but should be 
recorded by the investigator in the subjects’ medical records.
Post-trial Access in the commercial setting
Prescribers will be expected to follow the normal post-marketing reporting requirements as 
applicable in their country.
&(/*(1(35235,(7$5<,1)250$7,21
intervals
intervals
essments
essments (s(
are crossin
are cross
± 3 day
± 3 day win
w
y
ry testing. 
testing. 
y
vents
vents
bed in Appe
bed in App
matatioion, pl
n, p
ndment 
ndment #6
r to
r to Celgen
Cel
igators’ kno
gators’ kno
wri
written repo
tten repo
i
lgene) i
lgene) is to
ess and tim
ess and tim
se events w
se events w
invest
investigato
igato
ccess in the
ccess in the
*(
bers will be
bers will be
icable in th
icable in th

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
79
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
(1(35235,(7$5<,1)250$7,21
$
0$7
250
25
)2
1)2
,1)
< ,1
< ,1
5<
$5<
7$5
7$
(7$
5,(7
235
523
35
( 3
1(
(1(
*(1
*(
/*
(/*
&(/
&(
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
80
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
&(/*(1(35235,(7$5<,1)250$7,21
0$
50$
250
25
)25
1)2
5<
$5<
7$5
(7$
,(7
5,(7
35,
235
523
52
352
( 35
1(3
1(
(1
*(
/*(
(/*
&(/
(/

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
81
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
 
 
 
 
 
 
 
 
 
 
 
&(/*(1(35235,(7$5<,1)250$7,21
0$7
0$
50
250
25
)2
5<,
$5<
(7$
5,(7
5,(
35,
235

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
82
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
15.
STATISTICAL ANALYSES
The objective of the statistical analyses will be to investigate the efficacy and safety of 
lenalidomide monotherapy in patients with relapse or refractory mantle cell lymphoma.
Following the approval of Protocol Amendment #6 and closure of the clinical database, no 
efficacy or safety analyses will be performed for the subjects in the Extended Access Phase.
15.1.
Study Population Definitions
The primary efficacy analyses will be performed on the Intent-to-Treat Population (ITT) for the 
primary and secondary endpoints. Sensitivity analyses will be conducted for the primary and 
secondary endpoints based on the Full Analysis Set (FAS), and the Per Protocol set (if the PPS 
population differs ≥10% in size from the FAS). 
The safety analyses will be conducted on the treated set.
15.1.1.
Intent-to-Treat Population (ITT)
All randomized patients. 
15.1.2.
Treated Set 
All enrolled patients who receive at least one dose of study drug.
15.1.3.
Full Analysis Set (FAS)
The population will include all randomized patients that have received at least one single 
treatment dose (C1D1) with centrally confirmed histology of mantle cell lymphoma as well as 
documented progression at entry.
15.1.4.
As Treated population
The As Treated population analysis set is defined as all randomized patients who receive at least 
two cycles of treatment regardless of the treatment arm.
This population will be used for exploratory analysis only, for the following endpoints: PFS, 
ORR and OS.
15.1.5.
Per-protocol Set (PPS)
Per-protocol population is defined as all MCL randomized subjects who have met eligibility 
criteria, who received at least one dose of study treatment and who had at least one valid post 
baseline response assessment without any major protocol violation.
If the FAS population and the PPS population differ <10% in size no analysis will be conducted 
on the PPS population but if the PPS population differs ≥10% in size from the FAS, the 
sensitivity analysis on the primary endpoint will be conducted on the PPS population.
&(/*(1(35235,(7$5<,1)250$7,21
r the
the
and 
nd 
f the
the PPS 
PPS 
drug.
drug.
ts that have
ts that have
d histol
histology
og
s set is defi
et is def
ss 
ss of
of th
the tr
e tr
d for explor
d for expl
tocol Set
col Set (
opulat
pulatioion is
 received a
 received 
esponse as
ponse as
FAS
FAS popu
pop
the PP
he PPS po
po
sensit
ensi ivit
ivity

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
83
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
15.1.6.
Subgroup analysis
Subgroup analyses will be conducted in an exploratory manner for the following endpoints PFS, 
ORR and OS in the following subgroups:
!
Time since diagnosis (<3 years or ≥ 3 years)
!
Time since last treatment (<6 months [refractory] or ≥ 6 months)
!
Prior stem cell transplant (yes or no)
!
Age (< 65, ≥ 65) and gender
!
MCL International Prognostic Index (MIPI) score at initial time of diagnosis 
!
MIPI score at randomization
!
Ki-67 index (as defined by Determann, 2008) labeling in the original pathology 
specimen at diagnosis, if available at time or at time of relapse
!
Absolute lymphocyte count at baseline (< 800/mm3 or ≥ 800/mm3)
!
Time since last rituximab to cycle 1 day 1 (< 230 days or ≥ 230 days)
!
Number of prior treatment lines (with description of treatment regimens, including 
first line treatment and stem cell transplant) (1 vs >1), (<2 vs ≥2), (<3 vs ≥3)
!
Number of relapses (1 vs > 1 relapses), (<2 vs ≥2 relapses), (<3 vs ≥3 relapses)
In addition other potential subgroups or prognostic factors may be used as exploratory analyses, 
to be further detailed in the statistical analysis plan.
15.2.
Efficacy Evaluation
15.2.1.
Primary Efficacy Endpoints
Progression-free survival (PFS)
PFS is defined as the time from randomization to the first observation of disease progression or 
death due to any cause. If the patient has not progressed or died, PFS will be censored at the time 
of last completed assessment when the patient was known not to have progressed. Patients who 
will receive a new treatment without documented progression will be censored at the last 
assessment date that the patient is known to be progression-free (see table below).
Censoring Rules for Time to event (Progression and/or Death) Endpoints
Situation
Date of Progression or Censoring
Situation 
Outcome
No baseline assessments
Randomization
Censored
Progression documented 
First adequate assessment determined by 
central review
Progressed
&(/*(
n
*(1(35235,(7$5<,1)250$7,21
al pathology
l patholo
/mm
mm3)
≥ 230 day
≥ 230 day
f treatment r
treatm
>1), (<2 vs
>1), (<2 v
vs ≥2 rel
≥2 relap
ap
factors may
factors ma
an.
nts
nts
m rando
m randomi
m
the patient h
e patient 
ment 
me
when
whe
eatment wit
atment w
hat the patie
hat the patie
ules for Ti
es for T
*(
No baseli
No baseli
(/
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
84
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
No progression
Date of last adequate assessment with 
evidence of no progression
Censored
Study discontinuation for reasons other 
than disease progression or death
Date of last adequate assessment with 
evidence of no progression
Censored
New anti-lymphoma
/non-protocol treatment started prior to 
progression
Date of last adequate assessment with 
evidence of no progression prior to the 
start of new anti-lymphoma treatment
Censored
Death before first PD assessment while 
on study
Date of death
Progressed
Death between adequate assessment 
visits 
Date of death
Progressed
Death or progression after an extended 
lost-to-follow-up time (two or more 
missed assessments) 
Date of last adequate assessment with 
evidence of no progression
Censored
As additional robustness checks of the primary endpoint and censoring definition, the time to 
event analysis will be repeated for the ITT population using the following modified methods of 
PFS:
a) Using the investigator assessment instead the IRC central review 
b) Considering progression or death under a new anti-lymphoma treatment as an event
c) Considering death or progression after an extended lost-to-follow-up time (two or more 
missed assessments) as an event 
d) One using the earliest progression date either in investigator set or IRC set.
Efficacy analysis will be conducted one year after the last patient is randomized.
15.2.2.
Secondary Endpoints
Overall Response
The primary response rate will include best response of Complete Response (CR), Complete 
Response unconfirmed (CRu), or Partial Response (PR). The Modified International Workshop 
Response Criteria (IWRC) (Cheson, 1999) will be used and response assessed by CT scan with 
contrast /MRI with contrast every 56 days (± 7 days) for the first 6 months and then every 90 
days ± 15 days thereafter.
Patients who discontinue before any post-randomization efficacy assessments will be considered 
non-responders.
&(/*(1(35235,(7$5<,1)250$7,21
7,2
Progress
Progres
0$
50
25
essment wit
ssment w
ssion
io
1)
5<
nt and censo
nt and cens
n using the
n using t
d the IRC ce
d the IRC c
der a new a
der a new a
n after an ex
after an
ent 
nt 
gression da
gression d
conducted 
conduct
ary Endpo
ary Endpo
nse
nse
(
ry response
response
y
se unconfir
se unconfir
ponse Criter
ponse Crite
ntrast
ntrast /MR
MR
days ± 15
days ± 15
tien

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
85
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Duration of Response
Duration of response will be measured from the time of initial response (at least PR) until 
documented tumor progression or death. Patients who do not progress at the time of analysis will 
be censored at the last assessment date that the patient is known to be progression-free. Patients 
who will receive a new treatment without documented progression will be censored at the last 
assessment date that the patient is known to be progression-free.
This analysis will be restricted to the subgroup of responding patients.
Tumor control rate
Rates for Complete Response (CR) / Complete Response unconfirmed (CRu), Partial response 
(PR) / and Stable Disease (SD)
Complete response/ Complete response unconfirmed /Partial response/Stable disease will be 
determined using the Modified International Workshop Response Criteria (IWRC) (Cheson,
1999; Kane, 2007; Fisher, 2006).
Duration of Stable Disease
Stable disease is defined as less than a PR but is not progressive disease or relapsed disease.
Duration of stable disease will be calculated as the time from the first evidence of stable disease 
to documented disease progression or documented response or death. Patients who do not 
progress or respond at the time of analysis will be censored at the last assessment date that the 
patient is known to be progression-free. Patients who will receive a new treatment without 
documented progression will be censored at the last assessment date that the patient is known to 
be progression-free.
This analysis will be restricted to the subgroup of stable disease patients.
Time to progression (TTP)
TTP will be defined as the time from randomization until objective tumor progression; TTP will 
not include deaths. Patients without progression at the time of analysis will be censored at the 
last assessment date that the patient is known to be progression-free. Patients who will receive a 
new treatment without documented progression will be censored at the last assessment date that 
the patient is known to be progression-free. Deaths due to progression of disease will be 
considered as an event.
Time to treatment failure (TTF)
TTF is defined as the time from the first dose of study drug to discontinuation of treatment for 
any reason, including disease progression, treatment toxicity or death. Patients who will be on 
drug or complete the treatment according to the protocol will be censored at the last date of drug 
intake.
Time to tumor response (TTR)
Time to tumor response (TTR) will be defined as the time from randomization until initial 
response (CR, CRu, PR) if it has been confirmed. Patients with progression at the time of 
analysis will be censored at the first assessment date that the patient is known to have 
&(/*(1(35235,(7$5<,1)250$7,21
sponse
onse
ease will be
ease will be
WRC) 
RC (Ches
Che
sease or rel
sease or r
he first evid
e first
or death. P
or death. P
ed ata the la
the
will receive
will receiv
assessmen
assessme
oup of
up of stabl
stabl
m rando
randomiz
m
out progres
out progre
atient
atient is kn
is k
umented pr
mented p
be progress
be progre
nt.
nt.
t failure
t failure (T
(T
(1
ed as
ed as th
the tim
e ti
n, including
including
r complete 
r complete 
ke.
ke.
Time to tum
Time to tu
&(
ime t
ime t

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
86
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
progressed. Patients with SD at the time of analysis will be censored at the last assessment date 
that the patient is known to be progression-free.
Overall Survival (OS)
Overall survival will be defined as the time from randomization until death from any cause. 
Patients alive or lost to follow up at the time of analysis will be censored at the last date the 
patient was known to be alive.
Quality of Life
Background:
Health-related quality of life (QoL) is recognized to be an important element in the treatment of 
cancer patients. Over the last two decades, there has been an major progress in the development 
of robust validated tools to measure the QoL of cancer patients being used both before and 
during cancer treatments. QoL studies are becoming routinely used in the overall setting of 
clinical studies in oncology. 
Several QoL tools have been developed and validated; Two of the most widely used ones are the 
EORTC QLQ-C30 measure (Aaronson, 1993) as well as the functional assessment of cancer 
therapy (FACT-G). Of these two measures, the most frequently used and cited is the EORTC 
QLQ-C30 which has been most widely used in Europe (Bottomley, 2006; Fallowfield, 2002; 
Garret, 2002; Taphoorn, 2005). Meanwhile, they are recognized tools both by European and 
American regulatory authorities and the EORTC tool has been translated into over 70 languages, 
making it a valuable tool for international studies (Cull, 2002)
Rationale and objective:
QoL is important in relapsed and refractory MCL patients because cure is virtually not 
achievable and survival is poor. Therefore, the tolerability of a palliative intended treatment 
becomes even more important to maintain patients QoL as long as possible.
Commonly, patients with relapsed or refractory MCL often present with constitutional 
symptoms, such as asthenia, fatigue, weight loss and B-symptoms (including fever and night 
sweats). 
The EORTC QLQ-C30 measure will be used in this study, given it is robust and will address the 
key issues in these patients. The expectations are that lenalidomide may improve the global 
health status score as well as the physical functional score. The fatigue item could be worse 
initially under lenalidomide, but may improve mid and long term in responding patients due to 
tumor control in relation to the control arm with expected shorter response duration.
The primary QoL objective is therefore to determine the impact of lenalidomide on overall 
health/QoL. The H0 hypothesis will be tested that there is no difference in both arms during and 
after the treatment. 
A secondary QoL objective is to evaluate the effect of the treatment of various symptoms and 
functioning scales, with the two key ones being physical functional and fatigue. 
&(/*(1(35235,(7$5<,1)250$7,21
tment of 
tment of 
developmen
evelopme
efore and 
fore and 
rall setting 
ll setting
t widely us
t widely u
nalal assessm
assessm
sed and cit
ed and cit
mley, 2006
mley, 20
nized tools 
zed tools 
s been tran
been tra
ll, 2002
, 2002)
MCL pati
MCL patien
en
, the tolerab
e tolerab
ain pat
in patientn
or refractor
refracto
gue, weigh
gue, weigh
measure wil
easure 
ients. The
ents. The
as well as th
as well as t
nalido
nalidomide
mid
in rel
n relata ioion
ary Q
y
oL ob
/QoL. The 
/QoL. The 
r the treatm
r the treatm
A seconda
A seconda
unct
unctioio
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
87
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
QoL instrument: EORTC QLQ-C30 (see attachment Appendix 21.12)
The version 3.0 of the EORTC QLQ-C30 is a 30-item scale. The EORTC QLQ-C30 is composed 
of both multi-item scales and single-item measures. These include five functional scales, three 
symptom scales, a global health status / QoL scale, and six single items. 
FUNCTIONAL 
SCALES
(16 questions)
SYMPTOM SCALES
(6 questions)
SINGLE ITEMS
(6 questions)
GLOBAL QUALITY 
OF LIFE
(2 questions)
Physical
Fatigue
Constipation
Global QoL
Role
Pain
Diarrhoea
Cognitive
Nausea/vomiting
Sleep
Emotional
Dyspnoea
Social
Appetite
Financial
All of the scales and single-item measures range in score from 0 to 100. A higher scale score 
represents a higher level of well being and better ability of daily functioning. A 10 point change 
in the scoring is considered to be meaningful change in quality of life (Osoba, 1998).
Thus a high score for a functional scale represents a high/healthy level of functioning; a high 
score for the global health status/QoL represents a high QoL, but a high score for a symptom 
scale/item represents a high level of symptomatic problems.
Data collection and timing
Questionnaires must be filled out by the patient at 6 pre-specified time points (see below and
Table 2) when the patient comes for a scheduled visit. They will be handed out by a nurse or the 
treating physician/investigator, and ideally are collected again soon after the patient has filled it 
out.
Patients will be asked to complete the questionnaire as completely and accurate as possible. The 
average time to complete the questionnaire is around 10-15 minutes. The reasons for not 
completing the questionnaire will be recorded
Quality of life will be assessed at 6 time points (refer to Table 2)
!
at screening/baseline (within 7 days prior to randomization), 
!
after cycle 2 (C3D1)
!
after cycle 4 (C5D1),
!
after cycle 6 (C7D1),
!
after cycle 8 (C9D1),
!
and at time of discontinuation from treatment
A ± 7 days time window will be allowed.
&(/*(1(35235,(7$5<,1)250$7,21
7
$7
$7
$7
$7
0$
50
25
)2
1)
100. A hig
100. A h
funct
func ioning
in
y y of
of l
f ife (
ife (O
/healt
healthy 
hy lev
l
h QoL, but 
h QoL, but 
robl
roblems.
em
tient at 
ient at 6 p
cheduled vi
heduled 
deally are c
deally ar
lete the qu
lete the qu
he question
e questio
naire will
naire will b
e assessed 
assessed
reening/bas
reening/ba
after cy
ter cy
f
cle 
cle 
!
aftfter c
er c
!
afaf
!

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
88
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Compliance & Missing data
During the study compliance will be investigated at each time point. Compliance rate will be 
descriptively compared between the 2 arms. 
In the case that a patient still on study has not filled in the questionnaire, no more than ± 7 days
delay is accepted.
The rate of compliance will be assessed after 40, 80, 120 and 200 patients enrolled.
Missing data will be reported as recommended in the EORTC scoring manual (Fayers, 2001). 
!
Scales scores: If at least 50% of the items have been answered, the scale scores will 
be calculated according to the standard equations given on the manual (any items 
with missing values will be ignored). In other cases, scores will be set to missing
!
Single-item measures: the score will be set to missing 
Statistical considerations
No calculation in terms of sample size will be performed based on changes in QoL.
In the absence of more specific hypothesis, the global score will be used as the primary QoL
outcome and physical functional score and fatigue item will be used as secondary outcomes.
Expectations are that the global score and the physical functional score are improved by 
lenalidomide. The fatigue item may be worse initially under lenalidomide, but improve in mid 
and long term in responding patients due to tumor control compared to control arm with shorter 
response duration.
A difference of 10 points between the two arms is considered as clinically significant (Osoba, 
1998).
15.2.3.
Analysis Methods
All efficacy analyses will be conducted on intent to treat basis.
All efficacy analyses will be repeated on the Full Analysis Set (FAS) as sensitivity analysis for 
the primary endpoint.
The primary analysis for PFS to be performed on the ITT and FAS populations will be conducted 
one year after the last patient is randomized.
The Kaplan-Meier procedure will be used to characterize time to event endpoints (e.g., PFS, 
TTP, TTR, OS) and duration of response. Median times-to-event and their respective two-sided 
95% confidence intervals will be provided for each of these variables. 
The stratified log-rank test will be used as the main analysis to compare treatment arms for time-
to-event variables and an unstratified log-rank test will be used as supportive analysis. The Cox 
proportional hazards regression model will be used to assess the significance of stratification 
factors on treatment differences. Any demographic or baseline characteristics variables 
considered as strong predictive or prognostic factors will also be included as part of the formal 
statistical analysis plan.
&(/*(1(35235,(7$5<,1)250$7,21
s will
s will
items
items
missing
missing
nges in Qo
nges in QoL
used as the
used as t
used as seco
used as sec
ioional score
nal score
der 
der lenalido
enalid
trol compa
trol compa
isis conside
consid
cted on int
ed on int
epeated 
epeated on 
on
r r PFS
PF to b
st pati
patient
ent isi
ier procedu
ier procedu
S) and dura
S) and dur
dence inter
ence inter
ratified log
ratified log
vent variab
vent variab
proporti
roportiona
ona
fac
actors o
tors 
nsi

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
89
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Patients who drop out of the study without being evaluated for will be counted as non-
responders. Responses from patients after they receive other anti-cancer treatments will be 
counted as non responder.
Secondary endpoints will be analyzed at the time of the primary analysis of response. An update
of the time to events endpoints and overall survival will be done at the end of the follow up. No 
adjustment for multiplicity will be applied.
The probability of response rates will be estimated using the proportion of patients with 
responses with exact two-sided 95% confidence intervals.
The EORTC QLQ-C30 will be analyzed using change from baseline and percentage of change 
from baseline according to the functional scores and the recommendations in the EORTC scoring 
manual.
The EORTC Reference Data Manual (Scott, 2008) will also be used to descriptively check 
comparability between patients in our trial and with other comparable populations. The response 
rate in the cross-over portion of patients in Arm B will be analyzed in a descriptive manner.
15.3.
Background and Demographic Characteristics
Summary statistics (mean, standard deviation, median, minimum and maximum) will be 
provided for those variables measured on a continuous scale.  The frequency distribution (n %) 
will be provided for those variables measured on a nominal scale.
15.4.
Study Drug
Dosage statistics (mean, median, standard deviation and range) will be provided. Timing and 
reasons for dose adjustments will be summarized.
15.5.
Concomitant Therapy
By-patient listings will be provided for all concomitant medications and therapies taken during 
the trial.  They will be coded and categorized by the WHO drug coding system and frequency 
summaries provided.
15.6.
Safety Evaluation
Data from the treated population will be included in the safety analyses.
Adverse event severity will be classified using the NCI CTCAE criteria, version 3.0.
Adverse event frequency will be tabulated by body system, and MedDRA term. 
In the by-patient analysis, a patient having the same event more than once will be counted only 
once. Adverse events will be summarized by worst NCI CTCAE grade. Adverse events leading 
to death or to discontinuation from treatment, events classified as NCI CTCAE grade 3 or higher, 
study-drug related events, and serious adverse events will be listed separately.
Second primary malignancies throughout the course of the study will be monitored as events of 
interest, and will be listed and be analyzed separately.
&(/*(1(35235,(7$5<,1)250
ipt
iptively ch
ively c
pululatatioions
n . T
a descriptiv
descripti
tics
c
mum and m
mum and m
ale.  The fr
ale.  The fr
minal
minal scale.
scale.
viat
viatioion and
n and
marized.
marized.
py
py
ded for all 
ded for all 
and catego
and catego
Evaluatio
valuati
eated popu
eated popu
nt severit
nt severity
e event freq
e event fre
he by
he by-patie
patie
nce. Adve
nce. Adve
to death 
o death
dy
d
50$7,21
hange
ange
TC scoring
TC scorin
50

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
90
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
The probability of dose reduction will be estimated using the proportion of patients with dose 
reduction.
Laboratory data will be graded according to NCI CTCAE severity grade.
The frequencies of the worst severity grade observed during treatment will be displayed in cross-
tabulations by baseline status.
Vital signs, ECGs and ECOG Performance Status will be summarized as appropriate.
Graphical displays will be provided where useful to aid in the interpretation of results.
15.7.
Interim Analyses
An independent external Data Monitoring Committee (DMC) will review ongoing safety data 
throughout the study and efficacy for futility at a pre-defined time point. Specifics are outlined in 
the DMC charter. Summaries of safety information will be prepared for Data Monitoring 
Committee (DMC) review. The first safety analysis will occur after the first 40 patients have 
received at least 2 cycles of treatment or have discontinued prior to completing 2 cycles.  The 
second safety analysis as well as an efficacy analysis for futility will occur after 80 patients 
complete 2 cycles or withdraw before completing 2 cycles (around 54 patients in the 
lenalidomide arm). A third safety analysis will occur after 120 patients complete 2 cycles or 
withdraw before completing 2 cycles. A fourth safety analysis will occur after 200 patients 
complete 2 cycles or withdraw before completing 2 cycles. Additional efficacy and safety data 
might be provided to the DMC members on request as outlined in the DMC charter.
DMC will conduct an analysis for futility on PFS and Overall response rate. No specific stopping 
rules will be given to the DMC for the PFS, the following rules might be used for overall 
response rate.
Based on a 95% CI approach, if the upper bound is below 20% in the lenalidomide arm, the 
DMC should recommend stopping the trial.
Frequency 
of response
Binomial 
Proportion 
P
Exact Lower
CL, Binomial
Proportion1
Exact Upper
CL, Binomial
Proportion1
1
1.8519
0.04687
9.8915
2
3.7037
0.45173
12.7472
3
5.5556
1.16068
15.3885
4
7.4074
2.05510
17.8933
5
9.2593
3.07528
20.3002
6
11.1111
4.18838
22.6313
7
12.9630
5.37430
24.9012
8
14.8148
6.61976
27.1198
9
16.6667
7.91544
29.2941
10
18.5185
9.25455
31.4297
1 Exact confidence intervals based on the Clopper-Pearson method
&(/*(1(35235,(7$5<,1)250$7,21
afet
afety y data
data
s are outlin
s are outlin
Monitoring
onitoring
t 40 patient
t 40 patien
pleting
eting 2 cy
occur after 
occur after 
d 54 patient
54 patien
patients com
atients com
isis will
wil occ
cc
. Addit
Additioion
outlined in
outlined in
and Overall
and Overall
following 
following
er bound is 
er bound is 
e trial
e trial.
inomial
inomial
Proportion
Proportio
P
23
1
3
(
1(
1(
1(
1(
1(
4
(1
5
*
6
/*
&(
&

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
91
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
The third DMC recommended an increase of sample size. An adjustment of the alpha level for 
the final analysis is needed. The type I error will be controlled with adequate methods and details 
will be further described in the SAP.
15.8.
Sample Size and Power Considerations
The main objective of the study is to demonstrate the efficacy of lenalidomide over an 
investigator’s choice single agent based on PFS. The primary analysis is to compare PFS 
between lenalidomide and investigator’s choice monotherapy. 
Protocol Amendment #4:
The third independent DMC meeting was held on July 22, 2011, in which the committee 
members reviewed un-blinded both safety and efficacy data from 166 randomized patients. No 
safety concerns were noted.  The DMC observed that the interim PFS in the control arm is 
different from the intial assumptions which were used to calculate the sample size described in 
Protocol Amendment #2.  
The DMC therefore recommended increasing the sample size from 174 (number of patients 
randomized at the time of the DMC was held) to 250 patients and conducting the underpowered 
primary analysis one year after the last patient being randomized. This would allow a more 
reliable estimation of the treatment effect aiming at demonstrating a clinically meaningful 
improvement in PFS between the experimental arm and the control arm. In addition the proposed 
timing for the analysis will allow a reasonable follow up for overall survival so full information 
on the clinical benefit of lenalidomide can be provided at the time of PFS analysis.
The type I error will be controlled with adequate methods and the details will be further 
described in the SAP.
Protocol Amendment #2
With a hazard ratio of 1.7, full information necessary for a one-sided log rank test with an 
overall alpha of 0.025, to have 80% power, will be achieved when approximately 128 patients 
have progressed or died (PFS).
Original Protocol
The sample size of this study was originally calculated to estimate the Overall Response Rate 
(ORR), which was the original objective of the study.  Sample size calculation was based on the 
width of the 95% confidence interval around a certain point estimate for ORR that is considered 
significant clinical activity. Based on preliminary data, a response rate in the range of 30% to 
40% was reasonably expected.  A sample size equal to 100 allows us to construct a two sided 
95% confidence interval with a width of 9% (one direction) for an expected proportion of 30%. 
The lower observed confidence interval limit would be about 21%, which was still considered 
clinically meaningful. This sample size allowed a width (one direction) of 9.6% for an expected 
proportion of 40% and 9.3% for an expected proportion of 35% (See Table 10).
&(/*(1(35235,(7$5<,1)250$7,21
ee
ee
patients. No
patients. N
rol arm is
ol arm is
size
size descri
descr
(number 
(number
onducting t
ducting t
. This wou
This wou
ating a clini
ating a cl
control
control ara
p fo
p for overal
r overa
ed at the tim
ed at the tim
methods an
methods a
atatioion nece
n n
% power, w
power, w
study
study was 
was
e ori
original
ginal
confidence
confidence
ical activit
ical activ
asonably ex
asonably ex
fidence inte
ence inte
ower observ
wer observ
nically mea
ically mea
proporti
proportion 
on 

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
92
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 10:
Confidence Intervals
95% Two-Sided Confidence Intervals (N=100)
Response rate
30%
35%
40%
CI1
0.214 – 0.400
0.257 – 0.452
0.303 – 0.503
1 Exact confidence intervals based on the Clopper-Pearson method
Using a one group χ2 test with a 0.050 two-sided significance level a sample size of 100 patients 
will have 81% power to detect the difference between the Null hypothesis proportion of 20% and 
the alternative proportion of 32%. No formal sample size calculation will be done for the control 
arm. With a 2:1 ratio 50 patients are needed in the control arm. Assuming that 10% of patients 
will be lost to follow up, 167 patients were to be randomized.
15.9.
Other Topics
Exploratory Analyses:
Any subgroup analysis will be conducted on exploratory data.
Statistical tests will be performed to compare the two treatment arms only for exploratory 
purpose for the secondary endpoints.
Exploratory analysis will be conducted also on the As Treated population for the following 
endpoints: PFS, ORR and OS. 
In order to evaluate the effect of cross over on overall survival a Mantel-Byar approach will be 
used. The estimation of the control arm without cross over and the mixed arm (Lenalidomide
arm and cross over patients) will be estimated. A weighted logrank test or wilcoxon test will be 
used to take into account the cross over effect (Anderson, 1983; Klein, 1997; Colett, 2003)
Multivariate models will be used to identify those baseline and prognostic factors (e.g. absolute 
leukocyte count, time from diagnosis, number of prior therapies and any other variables 
suggested in the literature prior to the analysis) most predictive of response (Colett, 1991).
Mann-Whitney tests for simple comparison and longitudinal data modeling techniques (i.e. Proc 
mixed in SAS) for the QOL score. Details will be given in the statistical analysis plan.
&(/*(1(35235,(7$5<,1)250$7,21
and 
and
ontrol
ontrol
patients
patients
ms s only for
nly fo
ted populat
ed popul
ll survival 
ll surviva
cross over a
ross over 
. A weighte
. A weighte
ctct (Anders
Ander
ntify those
ify thos
s, number 
s, numbe
o the analys
o the analy
ple co
ple compar
mp i
OL score
score. D

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
93
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
16.
QUALITY CONTROL AND QUALITY ASSURANCE
16.1.
Monitoring 
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study.  Before the study is initiated at a site visit or at an investigator meeting, all aspects of 
the study are reviewed with the Investigator and the staff.  Prior to enrolling study patients into 
the study, a Celgene representative will review the protocol, data collectors, procedures for 
obtaining informed consent, record keeping, and reporting of AEs/SAEs with the Investigator.  
Monitoring will include on-site visits with the investigator and his/her staff as well as any 
appropriate communications by mail, email, fax, or telephone.  At each monitoring visit, the 
facilities, study drug storage area, Case report forms (CRFs), study patient’s source documents, 
and all other study documentation will be inspected and reviewed by the Celgene representative 
for accuracy, adherence to the protocol and Good Clinical Practice.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation.  Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff.  Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified.  Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene.  From time to time, representatives of this unit will conduct audits of 
clinical research activities in accordance with Celgene Standard Operating Procedures (SOPs) to 
evaluate compliance with Good Clinical Practice (GCP) guidelines and regulations.
The Investigator(s) is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of patient participation for audits and 
inspections by IRB/IECs, regulatory authorities (e.g. FDA, EMEA, and HC) and company 
authorized representatives.  The Investigator(s) should make every effort to be available for the 
audits and/or inspections.  If the Investigator(s) is contacted by any regulatory authority 
regarding an inspection, he/she should contact Celgene immediately.
16.3.
Investigator(s) Responsibilities
Investigator responsibilities are set out in the ICH guideline for Good Clinical Practice and in the 
US Code of Federal Regulations.  Celgene or a representative will contact and select all principal 
investigators or co-investigators who in turn will select their staff.  The investigator must give 
the monitor access to relevant records to confirm the above.  
The Investigator(s) is responsible for keeping a record of all patients who sign an Informed 
Consent Form and are screened for entry into the study.  For those patients who fail screening the 
reason(s) for exclusion must be recorded in the patient’s source documents and on the Screening 
Log provided by Celgene.
&(/*(1(35235,(7$5<,1)250$7,21
the
he
ocuments,
cuments,
epresentati
epresentati
rect com
rect compa
p
m
atioion.  Any
n.  A
ff.  Any ne
ff.  Any ne
Invest
estigato
iga
herence to i
herence to i
ng be verifi
ng be verif
moninitori
tori
i
ng 
ng
, a Good C
, a Good C
e, represent
e, represen
with Celgen
with Celgen
l Practice
Practice (
ermit direct
mit direc
plicable s
plicable su
ulatory
ulatory aut
aut
y
.  The Inve
The Inve
s.  If the In
s.  If the I
on, he/she 
n, he/she
vestigator
estigat
or responsib
responsib
de of Federa
e of Feder
stigators or
stigators o
e m
e moni
onitor a
or a
i
The Inve
The Inv
nse

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
94
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
No procedure/assessment/measurement/test other than those outlined here, or in the schedule of 
study assessments, is to be performed without the prior written approval of Celgene, or unless 
deemed by the investigator(s) as necessary for the patient’s medical care.  Investigator(s) and/or 
authorized designee(s) must enter study data onto CRFs supplied by Celgene.  The data on the 
CRF will be recorded in an anonymous manner to protect the patient’s identity by using a unique 
identifier that will prevent personal identifiable information.
The Investigator(s), or a designated member of the Investigators’ staff, must be available at some 
time during monitoring visits to review data and resolve any queries and to allow direct access to 
the patient’s records (e.g., medical records, office charts, hospital charts, and study related 
charts) for source data verification.  The CRFs must be completed as soon as possible after the 
patient’s visit but no later than prior to each monitoring visit and be made available to the 
Celgene representative(s) so that the accuracy and completeness may be checked.
Following the approval of Protocol Amendment #6 and closure of the clinical database, clinical 
study data will no longer be collected on CRFs by the investigator in the Expanded Access 
Phase. The investigator will be required to complete the subjects’ Drug Accountability and 
Dosing Record Sheet at each subject visit, as well as to verify and assure appropriate filing in 
study files, and in subjects’ medical records
&(/*(1(35235,(7$5<,1)250$7,21
toto
er the
r the
ththe
atabase
atabase, cl
pan
panded Acc
ded A
Accountabil
ccount
ure appropr
ure approp

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
95
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
17.
REGULATORY CONSIDERATIONS
17.1.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
The protocol for this study has been designed in accordance with the general ethical principles 
outlined in the Declaration of Helsinki (see Appendix 21.2).  The review of this protocol by the 
IRB/IEC and the performance of all aspects of the study, including the methods used for 
obtaining informed consent, must also be in accordance with principles enunciated in the 
declaration, as well as ICH Guidelines, Title 21 of the Code of Federal Regulations (CFR), Part 
50 Protection of Human Patients and Part 56 Institutional Review Boards.  Before implementing 
this study, the protocol, the proposed informed consent form and other information to patients, 
must be reviewed by a properly constituted Institutional Review Board/Independent Ethics 
Committee (IRB/IEC).  A signed and dated statement that the protocol and informed consent 
have been approved by the IRB/IEC must be given to Celgene before the study initiation.  The 
names and occupations of the chairman and the members of the IRB/IEC must be supplied to 
Celgene.  
The Investigator(s) will be responsible for preparing documents for submission to the relevant 
IRB/IEC and obtaining written approval for this study.  The approval will be obtained prior to 
the initiation of the study.
A copy of the IRB/IEC approval for the protocol and the Informed Consent is to be provided to 
Celgene. The approval for both the protocol and informed consent must specify the date of 
approval, protocol number and version, or amendment number.
The Investigator(s) is responsible for notifying the IRB/IEC of any serious deviations from the 
protocol, or anything else that may involve added risk to patients.
Any advertisements used to recruit patients for the study must be reviewed and approved by 
Celgene and the IRB/IEC prior to use.
17.2.
Protocol Amendments
Any amendment to this protocol that seems appropriate, as the study progresses (e.g. affects 
safety or efficacy) will be agreed upon between the coordinating and/or principal investigator(s) 
and the Celgene study physician.  Amendments will be submitted to the IRB/IEC for written 
approval before the implementation of the amended version.  The written signed approval from 
the IRB/IEC should refer specifically to the investigator(s) and to the protocol number and title 
and mention any amendment numbers that are applicable. Amendments that are administrative in 
nature do not require IRB/IEC approval but will be submitted to the IRB/IEC for information 
purposes.
17.3.
Informed Consent
The Investigator(s) must obtain informed consent of a patient or his/her designee prior to any 
study related procedures as per Good Clinical Practices (GCP) as set forth in the 21 CFR Parts 
50 and 56 and ICH guidelines.
&(/*(1(
dy
( 35235,(7$5<,1)250$7,21
Part 
art 
ement
enting 
ing
pati
patient
ents, 
s, 
nt Ethics
t Ethics
rmed conse
rmed con
dy init
dy ini iatatio
must be su
must be su
r submissio
r submiss
proval
roval will
l
l
e Informed 
Informe
rmed conse
med conse
ment numbe
ment numbe
g the IRB/IE
the IRB/IE
added risk 
added risk 
entnts for the
s for th
e.e.
dments
ments
otocol that 
ocol that
be agreed u
be agreed 
physician
physicia
y
he impleme
he impleme
hould refer 
ould refe
n any amen
n any amen
o not requir
ot requ
ses.
ses.
17.3.
7.3.
he In
he In

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
96
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Documentation that informed consent occurred prior to the patient’s entry into the study and of 
the informed consent process should be recorded in the patient’s source documents.  The original 
consent form, signed and dated by the patient and by the person consenting the patient prior to 
the patient’s entry into the study, must be maintained in the Investigator’s study files and a copy 
given to the patient.  In addition, if a protocol is amended and it impacts on the content of the 
informed consent, the informed consent must be revised.  Patients participating in the study when 
the amended protocol is implemented must be re-consented with the revised version of the 
informed consent.  The revised consent form signed and dated by the patient and by the person 
consenting the patient must be maintained in the Investigator’s study files and a copy given to 
the patient.  
17.4.
Patient Confidentiality
Celgene affirms the patient’s right to protection against invasion of privacy. In compliance with 
United States federal regulations, Celgene requires the Investigator(s) to permit Celgene’s 
representatives and, when necessary, representatives of the FDA or other regulatory authorities 
to review and/or copy any medical records relevant to the study in accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
patient’s statement of informed consent, it is the responsibility of the Investigator(s) to obtain 
such permission in writing from the appropriate individual.
&(/*(1(35235,(7$5<,1)250$7,21
o 
om
ompliance 
pliance 
m
mit Celgene
mit Celgene
egulatory
gulatory a
y
rdance wit
ance w h
zation sepa
zation sep
f the Invest
f the Inves

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
97
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
18.
DATA HANDLING AND RECORDKEEPING
18.1.
Data/Documents
The investigator(s) must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the study drug, that is copies of CRFs and source documents, 
original documents, data, and records (e.g., hospital records; clinical and office charts; laboratory 
notes; memoranda; patient’s diaries or evaluation checklists; pharmacy dispensing records; 
recorded data from automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiches; photographic negatives, microfilm, or magnetic media; x-
rays; patient files) and records kept at the pharmacy, at the laboratories, and at medico-technical 
departments involved in the clinical study are complete, accurate, and filed and retained.
18.2.
Data Management
Data will be entered into the clinical database per 
SOPs unless internal processes will be 
done by Data Management of Celgene, in this case Celgene SOPs will be used. This data will be 
electronically verified through use of programmed edit checks specified by the clinical team.  
Discrepancies in the data will be brought to the attention of the clinical team, and investigational 
site personnel, if necessary.  Resolutions to these issues will be reflected in the database.  An 
audit trail within the system will track all changes made to the data.
Extended Access Phase
Following the approval of Protocol Amendment #6, CRF pages will no longer be completed. At 
each visit, the study monitor will be required to verify and assure appropriate filing in study files 
of the subjects’ Drug accountability and Dosing Record Sheets and verify the information therein 
with the source records of the subject. The study monitor will record changes in the subjects’
Drug Accountability and Dosing Record Sheet in their visit report.
18.3.
Retention of Records
The Investigator must maintain records of all study documents and supporting information 
relating to the conduct of the study in accordance with ICH GCP and applicable local regulatory 
requirements.  This documentation includes, but is not limited to, protocols, case report forms, 
advertising for study patient participation, adverse event reports, study patient source data, 
correspondence with health authorities and IRBs/IECs, informed consent documents, 
Investigator curricula vitae, monitor visit logs, laboratory reference ranges, laboratory 
certification or quality control procedures and laboratory director curriculum vitae.  Study patient
files and other source data must be kept for the maximum period of time permitted by the 
hospital, institution or private practice specified below.  The study monitor or designee must be 
consulted if the Investigator wishes to assign the study files to someone else, remove them to 
another location or is unable to retain them for a specified period.  The monitor will inform the 
Investigator of the dates for retention.  All study documents should be made available if required 
by relevant health authorities. Investigator/Institution should take measures to prevent accidental 
or premature destruction of these documents.
For studies conducted in the United States under a US IND, the Investigator must retain the 
study records for a minimum of 2 years after a marketing application for the indication is 
&(/*(1(35235,(7$5<,1)250$7,21
s s 
x-
chnical
hnical
ed.
ernal proces
ernal proce
sed. This da
. Thi
ed by
ed by the c
the c
y
nical team, 
nical team
eflected in
eflected in
e data.
e dat
CRF pages
CRF pag
erify and as
erify and a
g Record
ecord S
tudy
tudy moni
moniti
Sheet 
Sheet inin thth
ds
n records of
records of
e study
e study i
y n a
n
mentati
tation i
pati
atient
ent parti
part
th healt
h health au
h au
ricula vitae
ricula vitae
or qualit
r quality y c
ther source
her source
, insti
, instituti
tuti
i
on
o
ulted if the
ulted if the
nother locat
nother locat
Invest
nvestigat
igat
y rele
rele

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
98
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
approved or for 2 years after the IND is withdrawn.  If no application is filed, or if the 
application is not approved for the indication, the records are to be retained for two years after 
the investigation (i.e., the IND) is discontinued, and FDA is notified of that fact.  For IND 
studies conducted outside the US, the Investigator must retain study records for the time period 
described above or according to local laws or requirements, whichever is longer.  For studies not 
conducted under the US IND, the Investigator records must be retained until at least 2 years after 
the last approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product.  These documents 
should be retained for a longer period if required by other applicable regulatory requirements.
&(/*(1(35235,(7$5<,1)250$7,21
nts 
nts 
nts.
nts.

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
99
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
19.
PREMATURE DISCONTINUATION OF THE STUDY
19.1.
Single Site
The responsible clinical Investigator as well as Celgene has the right to discontinue a single site 
at any time during the study for reasonable medical or administrative reasons.  Possible reasons
for termination of the study could be, but are not limited to:
!
Unsatisfactory enrollment with respect to quantity or quality
!
GCP noncompliance
∀
Inaccurate or incomplete data collection
∀
Falsification of records
∀
Failure to adhere to the study protocol
19.2.
Study as a Whole
Celgene reserves the right to terminate this clinical study at any time for reasonable medical or 
administrative reasons.
Any possible premature discontinuation would have to be documented adequately with reasons 
being stated, and information would be issued according to local requirements (e.g., IRB/IEC, 
regulatory authorities, etc.).
for reason
for reason
cumented a
umented
o local requ
ocal req

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
100
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
20.
REFERENCES
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organisation for Research and 
Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials 
in oncology. Natl Cancer Inst 1993; 85:365-376.
Armitage JO. Treatment of non-Hodgkin’s lymphoma. N Engl J Med. 1993; 328(14):1023-30. 
Andritsos L, Johnson AJ, Lozanski G, et al. Doses of Lenalidomide Are Associated With 
Unacceptable Toxicity Including Life Threatening Tumor Flare in Patients With Chronic 
Lymphocytic Leukemia. J Clin Oncol. 2008; 26(15):2519-2525.
Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response and other 
comparisons of time-to-event by outcome variables J Clin Oncol. 2008; 26(24):3913-5.
Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response J Clin Oncol. 1983; 
1(11):710-19.
Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, 
Jelliffe A, Vaughan G, Hudson , Linch DC; British National Lymphoma Investigation. Long-
term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic 
advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16; 
362(9383):516-22.
Bottomley A, Gaafa R, Manegold C, Burgers S, Coens C, et al. Short-term treatment-related 
symptoms and quality of life: results from an international randomized phase III study of 
cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an EORTC 
Lung-Cancer Group and National Cancer Institute, Canada, Intergroup Study. J Clin Oncol. 
2006; 24(9):1435-42.
Brookmeyer R, Crowley J. A Confidence Interval for the Median Survival Time. Biometrics. 
1982; 38(1): 29-41.
Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification.Br J 
Haematol. 2004 Oct; 127 (1):3-11
Chanan-Khan A, Miller KC, Musial L, et al. Clinical efficacy of lenalidomide in patients with
relapsed or refractory chronic lymphocytic leukemia : results of a phase II study. J Clin Oncol.
2006 Dec 1; 24(34):5343-9.
Chanan-Khan A, Miller KC, Whitworth A, et al. Clinical activity of lenalidomide in relapsed or 
refractory chronic lymphocytic leukemia (CLL) patients: updated results of a phase II clinical 
trial. Leuk Lymphoma. 2007; 48 (suppl 1): S166.
Cheson B, Horning S, Coiffier B, Shipp M, Fisher R, Connors J, et al. Report of an international 
workshop to standardize response criteria for non-Hodgkin's lymphoma. J Clin Oncol.1999; 17: 
1244-53.
Collett, D. Modelling Binary Data. 1991; London: Chapman & Hall. 
Collett, D. Modelling Survival Data in Medical Research Second Edition. 2003; London: 
Chapman & Hall.
-5.
n Oncol
n Oncol. 1
KA
KA, Marc
Marc
ma Invest
a Investiga
ig
eatment for
tment fo
d trial.
tri
Lan
La
et al. Shor
et al. Shor
nal rando
nal random
malignant 
alignan
e, Canada, 
e, Canada
Interval fo
Interval fo
s syndrome
yndrome
11
11
, Musial L
 Musial 
ronic lymp
ronic lym
343
343-9.9.
Miller KC,
Miller KC,
ninic lympho
c lymp
Lymphoma.
ymphoma.
B, Horning
B, Hornin
kshop to sta
kshop to st
44-53.
44-53.
Collett, D
Collett

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
101
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron
1976; 16: 31-41.
Cohen BJ, Moskowitz, Straus D, Noy A, Hedrick E, Zelenetz A. Cyclophosphamide/Fludarabine 
is active in the treatment of mantle cell lymphoma. Leuk Lymph. 2001; 42(5):1015-1022.
Clopper C, Pearson S. The use of confidence or fiducial limits illustrated in the case of the 
binomial. Biometrika 26: 404-413, 1934.
Corral L, Hasslet P, Muller GW, et al. Differential cytokine modulation and T cell activation by 
two distinct classes of thaliodimide analogues that are potent inhibitors of TNF-α. J Immunol. 
1999; 163: 380-386.
Cull A, Sprangers MAG, Bjordal K, Aaronson NK, West K, Bottomley A. Guidelines for 
translating EORTC Questionnaires. Brussels, Belgium, Quality of Life Study Group 
Publications, EORTC Publications, 2002
Czuczman MS, Reeder CB, Polikoff J, et al.  International Study of Lenalidomide in 
Relapsed/Refractory Aggressive Non-Hodgkin s Lymphoma).  J Clin Oncol 26: 2008 (May 20 
suppl; abstr 8509)
Damaj G., Lefere F, Delaure R, Varet B, Furman R, Hermine O. Thalidomide therapy induces 
response in relapsed mantle cell lymphoma. Leukemia. 2003; 17(9):1914-1915.
Decaudin D, Bosq J, Tertian G, Nedellec G, Bennaceur A, Venuat AM, Bayle C, Carde P, 
Bendahmane B, Hayat M, Munck JN. Phase II trial of fludarabine monophosphate in patients 
with mantle-cell lymphomas. J Clin Oncol. 1998 Feb;16(2):579-83.
Determann O, Hoster E, Ott G, Wolfram Bernd H, Loddenkemper C, Leo Hansmann M, Barth 
TE, Unterhalt M, Hiddemann W, Dreyling M, Klapper W; European Mantle Cell Lymphoma 
Network and the German Low Grade Lymphoma Study Group.Ki-67 predicts outcome in 
advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: 
results from randomized trials of the European MCL Network and the German Low Grade 
Lymphoma Study Group. Blood. 2008 Feb 15; 111(4):2385-7.
Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus Dexamethasone for Relapsed or 
Refractory Multiple Myeloma . New Engl J Med. Nov 2007; 357:2123-2132
Dreyling M, Lenz G, Hoster E, et al. Early consolidation by myeloblative radiochemotherapy 
followed by autologous stem cell transplantation in first remission significantly prolongs 
progression-free survival in mantle cell lymphoma: results of a prospective randomized trial of 
the European MCL network. Blood. 2005; 105(7):2677-2684.
Dumontet C, Morschhauser F, Solal-Celigny P, Bouafia F, Bourgeois E, Thieblemont C, Leleu 
X, Hequet O, Salles G, Coiffier B. Gemcitabine as a single agent in the treatment of relapsed or 
refractory low-grade non-Hodgkin's lymphoma. Br J Haematol. 2001 Jun;113(3):772-8.
Epner EM, Unger J, Miller T, Rimzsa L, Spier C, Leblanc M.  A multi center trial of                  
hyper CVAD + Rituxan in patients with newly diagnosed mantle cell lymphoma. Blood (ASH 
Annual Meeting Abstracts), Nov 2007; 110:387
Eve HE, and Rule SAJ. Lenalidomide-induced tumour flare reaction in mantle cell lymphoma. 
Br J Haematol. Nov 2010 151: 410–412.
&(/*(1(35235,(7$5<,1)250$7,21
y
l. . l
s for 
s for 
up
omide in 
omide in 
ncol
col 26: 20
26
Thalido
halidomid
mid
17(9):1914
17(9):19
Venuat A
Venuat A
ludarabine 
udarabine
b;16(2):579
b;16(2):5
H, Lodden
H, Lodden
M, Klapper W
, Klapper W
mpho
phoma 
ma Stu
Stu
patients tre
atients tr
European 
Europea
2008 Feb 1
2008 Feb
Attal M, et a
Attal M, et 
ma
ma . New
New E
w
Hoster E, et
Hoster E, e
gous stem
gous stem c
m
survival in
survival i
MC
MCL netw
L netw
t C, Morsch
C, Morsc
quet O, Sal
quet O, Sal
actory
actory l
y ow
ow
Epner EM
Epner EM
yper
yper C

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
102
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Fallowfield L, Gagnon D, Zagari M, Cella D, Bresnahan B, et al. Multivariate regression 
analyses of data from a randomised, double-blind, placebo-controlled study confirm quality of 
life benefit of epoetin alfa in patients receiving non-platinum chemotherapy. Br J Cancer. 2002;
87(12):1341-53.
Fayers P, Aaronson N, Bjordal K, Groenvold M, Curran D, Bottomley A. EORTC QLQ-C30 
Scoring Manual (ed 3). Brussels, Belgium, EORTC Publications, 2001
Fernandez V, Hartmann E, Ott G, Campo E, Rosenwald . Pathogenesis of mantle cell lymphoma: 
All oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways. J 
Clin Oncol. 2005; 23(26): 6364-6369. 
Fernandez V, Serrano S, Jares P, Campo E. Genomic and Gene Expression Profiling Defines 
Indolent Forms of Mantle Cell Lymphoma. Cancer Res. 2010 Feb 15; 70 (4):1408-1418.
Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, Wierda WG, Estrov Z, Faderl S, 
Cohen EN, Li C, Reuben JM, Keating MJ. Lenalidomide induces complete and partial 
remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008 
Jun 1; 111(11):5291-7.
Fisher RI, Bernstein SH, Kahl BS, et al. Mulicenter phase II study of bortezomib in patients with 
relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006; 24(30):4867-4874.
Foran JM, Rohatiner AS, Coiffier B, et al. Multicenter phase II study of Fludarabine phosphate 
for patients with newly diagnosed lymphoplasmacytoid lymphoma, Waldenstroms 
macroglobulinema, and mantle cell lymphoma. J Clin Oncol. 1999;17(2):546-553.
Fu K, Weisenburger DD, Greiner TC, et al. Cyclin D1-negative mantle cell lymphoma: a 
clincopathologic study based on gene expression profiling. Blood. 2005; 106:4315-4321
Gaidarova S, Corral LG, Gleizer E, Young D, Brady H, Bennett B, Lopez-Girona A. 
Lenalidomide enhances anti-tumor effect of γδ T cells against mantle cell lymphoma. Blood.
2008; 112:906, abstr 2616. 
Galustian, C, Labarthe MC, Barlett JB, Dalgleish AG. Thalidomide-derived immunomodulatory 
drugs as therapeutic agents. Expert Opin Biol Ther. 2004; 4(12): 1963-1970.
Garret A, Schmedit L, Mackintosh A, Fitzpatrick. Quality of life measurement: bibliographic 
study of patient assessed health outcome measures. BMJ.2002; 324:1417-1419.
Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, 
Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, 
Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, 
Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle 
cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell 
rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood.
2008 Oct 1;112(7):2687-93. [Epub 2008 Jul 14].
Ghielmini M, Schmitz SF, Bürki K, Pichert G, Betticher DC, Stupp R, Wernli M, Lohri A, 
Schmitter D, Bertoni F, Cerny T. The effect of Rituximab on patients with follicular and mantle-
cell lymphoma. Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol. 2000; 11 Suppl 
1:123-6.
&(/*(1(35235,(7$5<,1)250$7,21
:
J 
Defines
efines
1418.
418.
rov Z, Fad
rov Z, Fa
and partial
and partia
ukemia.
ukemia. B
of
o bortezom
ortezo
f
6; 24(30):4
6; 24(30):4
se II study
e II study o
y
lympho
ymphoma,
m
Oncol. 
Oncol. 19
19
n D1
n D1-negat
ega
on profiling
n profilin
g D, Brady
g D, Brady
ct of γδ T
t of γδ T
lett JB, Dal
lett JB, Da
Expert Opin
Expert Opin
ackintosh A
ackinto
ed healt
ed hea h o
ad A, Laur
d A, Laur
Kimby E,
Kimby E B
, Ehinger M
, Ehinger M
Elonen E; 
lonen E;
mpho
mph ma af
ma af
cue: a nonra
ue: a nonr
2008 Oct 1
008 Oct 1
Ghielm
Ghielm

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
103
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Goy A, Younes A, McLaughlin P, Pro B, Romaguera JE, Hagemeister F, Fayad L, Dang NH, 
Samaniego F, Wang M, Broglio K, Samuels B, Gilles F, Sarris AH, Hart S, Trehu E, Schenkein 
D, Cabanillas F, Rodriguez AM. Phase II study of proteasome inhibitor bortezomib in relapsed 
or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2005 Feb 1;23(4):667-75. [Epub 
2004 Dec 21].
de Guibert S, Jaccard A, Bernard M, Turlure P, Bordessoule D, Lamy T. Rituximab and DHAP 
followed by intensive therapy with autologous stem cell transplantation as first line therapy for 
mantle cell lymphoma. Hematologica. 2006; 91:425-426. 
Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K, Wride K, Ervin-
Haynes A, Takeshita K, Pietronigro D, Zeldis JB, Tuscano JM. Lenalidomide oral monotherapy 
produces a high response rate in patients with relapsed or refractory mantle cell lymphoma.Br J 
Haematol. Feb 2009, (Epub ahead of print).
Haritunians T, Mori A, O’kelly J, Luong QT, Giles FJ, Koeffler HP. Antipoliferative activity of 
RAD001(everolimus) as a single agent and combined with other agents in mantle cell 
lymphoma. Leukemia. 2007; 21:333-339.
Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F, 
Strahs A, Berkenblit A, Hanushevsky O, Clancy J, Hewes B, Moore L, and Coiffier B. Phase III 
Study to Evaluate Temsirolimus Compared With Investigator’s Choice Therapy for the 
Treatment of Relapsed or Refractory Mantle Cell Lymphoma. J Clin Oncol. 2009; 27:3822-
3829.
Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with 
advanced-stage mantle cell lymphoma. Blood. 2008; 111: 558-565
Jares P, Campo E. Advances in understanding of mantle cell lymphoma. J Haematology. 2008 
Apr 10. [Epub ahead of print]
Kane R, Dagher R, Farrell A, Ko C, Sridhara R, Justice R, Pazdur R. Bortezomib for the 
Treatment of Mantle Cell Lymphoma. Clin Cancer Res. 2007; 13(18): 5291-5294. 
Kantarjian H, Barlogie B, Plunkett W, Velasquez W, McLaughlin P, Riggs S, Cabanillas F. 
High-dose cytosine arabinoside in non-Hodgkin's lymphoma. J Clin Oncol. 1983 Nov;1(11):689-
94.
Kaufmann H, Raderer M, Wohrer S, et al. Antitumor activity of rituximab plus thalidomide in 
patients with relapsed/refractory mantle cell lymphoma. Blood. 2004; 104:2269-2271.
Klein J.P, Moeschberger ML. Survival Analysis: Techniques for Censored and Truncated Data, 
1997; New York: Springer-Verlag.
Kouroukis CT, Belch A, Crump M, et al. Flovopiridol in untreated or relapsed mantle cell 
lymphoma: Results of a phase II study of the national cancer institute of Canada clinical trials 
group. J Clin Oncol. 2003; 21:1740-1745.
List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the 
myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 
5;355(14):1456-65.
otherapy
otherapy
pho
phoma.
ma.Br J
Br J
ferat
ra ive act
ve ac
mant
mantle cell
le cell
echt C, Lau
ht C, Lau
ore L, and 
e L, and
’s Cho
s Choice T
ice
ma.a. J Clin O
J Clin
gnostic inde
gnostic in
008; 111: 5
08; 111: 5
g of
g of m
f
ant
antlele
Sridhara R, 
Sridhara
ma.a. Clin C
lin C
kett W
kett W, Ve
V
side in non
ide in no
er M, Wohr
r M, Woh
psed/refrac
psed/refrac
oeschberger
eschberge
w York: Spr
York: Spr
ukikis CT, B
s CT, B
mpho
phoma: Re
ma: Re
group. 
roup. J C
J Cl
C
List A, 
ist A,

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
104
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Luke DR, Halstenson CE, Opsahl JA, Matzke GR. Validity of creatinine clearance estimates in 
the assessment of renal function. Clin Pharmacol Ther. 1990; 48: 503-508.
Morschhauser F, Depil S, Jourdan E, Wetterwald M, Bouabdallah R, Marit G, Solal-Céligny P, 
Sebban C, Coiffier B, Chouaki N, Bauters F, Dumontet C. Phase II study of gemcitabine-
dexamethasone with or without cisplatin in relapsed or refractory mantle cell lymphoma. Ann 
Oncol. 2007 Feb;18(2):370-5. http://annonc.oxfordjournals.org/cgi/content/abstract/mdm463v1. 
Accessed 16 January 2008. 
Moutouh-de Parseval LA, Weiss L, DeLap RJ, Knight RD, Zeldis JB.Tumor lysis 
syndrome/tumor flare reaction in lenalidomide-treated chronic lymphocytic leukemia.J Clin 
Oncol. 2007 Nov 1; 25(31):5047.
Miller KC, Czuczman MS, DiMiceli L, et al. Antileukemic effects of novel immunomodulatory 
agent lenalidomide with or without rituximab in patients with relapsed or refractory chronic 
lymphocytic leukemia: encouraging preliminary results of an ongoing Phase II clinical study
.J Clin Oncol, 2005 ASCO Annual Meeting Proceedings. Vol 23, No. 16S, Part I of II (June 1 
Supplement), 2005: 6557
O’ Connor OA, Wright J, Moskowitz C, et al. Phase II clinical experience with the novel 
proteasome inhibitor Bortezomib in patients with indolent non-Hodgkin’s lymphoma and mantle 
cell lymphoma. J Clin Oncol. 2005; 23: 676-684.
Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in 
health-related quality-of-life scores. J Clin Oncol. 1998; 16(1):139-44
Pan D, Moskowitz CH,  Zelenetz AD, Straus D, Kewalaramani T, Noy A, et al. Rituximab for 
Aggressive Non-Hodgkin’s Lymphomas Relapsing After or Refractory to Autologous Stem Cell 
Transplantation. The Cancer Journal. 2002; 8(5): 371-376.
Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary 
therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343:1750–1757.
Ramsay AG, Johnson AJ, Lee AM, Gorgun G, Le Dieu R, Blum W, Byrd JC, Gribben JG. 
Chronic Lymphocyctic Leukemia T cells Show Impaired Immunological Synapse Formation 
That can be Reversed with an Immunomudulation drug. J. Clin. Invest. 2008 July 1; 118(7): 
22427-2437.
Ramsay AG, Clear AJ, Kelly G et al. Follicular lymphoma cells induce T-cell immunologic 
synapse dysfunction that can be repaired with lenalidomide: implications for the tumor 
microenvironment and immunotherapy. Blood. 2009; 114, (21) 4713-4720.
Schafer PH, Gandhi AK, Loveland MA, et al. Enhancement of cytokine production and AP-1 
transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol 
Exp Ther. 2003; 305(3):1222-1232.
Schlette E, Lai R, Onciu M, Doherty D, Bueso-Ramos C, Medeiros LJ. The US and Canadian 
academy of pathology, Inc. 2001; 14(11):1133-1140.
Scott NW, Fayers PM, Aaronson NK, Bottomley A, Graeff de G, Groenvold et al. EORTC 
QLQ-C30 Reference Values.  EORTC Quality of Life Group, EORTC publications 2008.
&(/*(1(35235,(7$5<,1)250$7,21
n
mo
modul
dulator
ato
ory
ory chronic
chronic
y
I clinical st
I clinical s
Part I of II
Part I of I
rience with
ence with
Hodgkin’s ly
dgkin’s l
ng the sign
ng the sign
8;8; 16(1):13
6(1):13
ewalarama
ewalarama
sing After o
ing After
8(5)
8(5): 371-3
371-3
t al.
al. Fludara
Fludar
mia.
mia. N Eng
N En
M, Gorgun 
M, Gorgun
mia T cells 
ia T cells
n Immuno
n Immun
AJ, Kelly G
J, Kelly G
on that can
n that can
ment and im
ent and i
H, Gandhi A
 Gandhi A
ptptional acti
nal act
Ther. 
Ther. 2003
2003
Schlette
lette E,
E,
academy
academ

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
105
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Taphoorn M, Stupp R, Coens C, Osoba D, Kortmann R, et al. Health-related quality of life in 
patients with glioblastoma: a randomised controlled trial. Lancet Oncol. 2005; 6(12):937-44.
Tobinai K, Watanabe T, Ogura M, Morishima Y, et al. Phase II study of oral fludarabine 
phosphate in relapsed indolent B-Cell non-Hodgkins lymphoma. J Clin Oncol. 2006; 24(1):174-
180.
UK SPC, UK Summary of Product Characteristics for Cytarabine Injection Solution 100mg/ml 
dated 26th April 2007 (Mayne Pharma plc).
Verhelle D, Corral LG, Wong K, et al. Lenalidomide and CC-4047 inhibit the proliferation of 
malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007;
67(2):746-755.
Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus Dexamethasone for Relapsed 
Multiple Myeloma in North America. New Engl J Med. Nov 2007. 357:2123-2132
Wiernik P, Lossos I, Tuscano J, Justice G, Vose J, et al. Lenalidomide Monotherapy in Relapsed
or Refractory Aggressive Non-Hodgkin's Lymphoma. J Clin Oncol. 2008 Jul 7.
Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P, et al. Phase II Trial of 
Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma. J Clin Oncol. 
2000; 23 (23): 5347-5356.
Witzig TE, Reeder CB, Polikoff J, et al.  Initial Results from an International Study in 
Relapsed/Refractory Aggressive Non-Hodgkin s Lymphoma to Confirm the Activity, Safety and 
Criteria for Predicting Response to Lenalidomide Monotherapy.  Blood (ASH Annual Meeting 
Abstracts), Nov 2007; 110: 2572.
Witzig TE, Vose JM., Zinzani PL, Reeder CB, Buckstein R, Polikoff J, Bouabdallah R, Haioun 
C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL and Czuczman MS. An international phase 
II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s 
lymphoma. Ann Oncol; 12 Jan 2011 [Epub ahead of print] 
Zhang LH, Schafer PH, Muller G, Stirling DI, Bartlett JB. Lenalidomide displays direct anti-
Hodgkin’s Lymphoma (NHL) activity in association with enhanced SPARC expression but 
independent of its ability to strongly inhibit NHL cell VEGF production in vitro. Blood (ASH 
Annual Meeting Abstracts), Nov 2007; 110: 3473. 
Zinzani PL, Magagnoli M, Moretti L, De Renzo A, Battista R, Zaccaria A, Guardigni L, Mazza 
P, Marra R, Ronconi F, Lauta VM, Bendandi M, Gherlinzoni F, Gentilini P, Ciccone F, Cellini 
C, Stefoni V, Ricciuti F, Gobbi M, Tura S. Randomized trial of fludarabine versus fludarabine 
and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma. J Clin 
Oncol. 2000 Feb; 18(4):773-9.
Zhu D, Corral LG, Fleming YW, Stein B. Immunomodulatory drugs Revlimid® (lenalidomide) 
and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell 
activation. Cancer Immunol Immunother. 2008 Apr 8. [Epub ahead of print].
&(/*(1(35235,(7$5<,1)250$7,21
f f 
elapsed 
lapsed 
32
32
notherapy
notherapy i
y
8 Jul 7
Jul 7.
et al. Phas
et al. Phas
Lympho
ymphom
m an Inter
an Inter
m
ho
homa to Co
ma to C
onoth
onotherapy
rap
B, Buckstei
B, Buckstei
aynes A
aynes AL
relapsed or
relapsed 
[Epub ahea
[Epub ah
G, Stirling 
G, Stirling 
) activit
) activity y inin
o strongly i
strongly 
cts), Nov 2
cts), Nov 
noli M
li M, , Mo
Mo
coni F
coni F, Lau
La
Ricciut
Ricciuti F
cin as fron
cin as fron
2000 Feb;
2000 Feb;
u D, Corral 
D, Corral
nd CC
nd CC-404
404
&
activat
ctivatioi

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
106
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.
APPENDICES
21.1.
Adverse Event
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence occurring at 
any dose that may appear or worsen in a patient during the course of a study. It may be a new 
intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment 
of the patient’s health, including laboratory test values (as specified by the criteria below), 
regardless of etiology. Any medical condition that is presented prior to study treatment and that 
remains unchanged or improved should not be recorded as an AE. If there is a worsening of that 
medical condition this should be considered as an AE. A diagnosis or syndrome should be 
recorded on the AE page of the Case Report Form rather than the individual signs or symptoms 
of the diagnosis or syndrome.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an investigational product should be reported as an AE.  If 
an overdose is associated with an AE, the overdose and adverse event should be reported as 
separate terms.
All subjects will be monitored for AEs during the study.  Assessments may include monitoring 
of any or all of the following parameters:  the subject’s clinical symptoms, laboratory, 
pathological, radiological or surgical findings, physical examination findings, or other 
appropriate tests and procedures.
All AEs will be recorded by the Investigator(s) from time of signed informed consent through 
the end (see Table 3 and Appendix 21.1.9) of the designated follow-up period. AEs will be 
recorded on the AE page of the CRF and in the patient’s source documents. All SAEs must be 
reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by 
facsimile, or other appropriate method, using the SAE Report Form, or approved equivalent 
form.
Following the approval of Protocol Amendment #6, only serious adverse event data (including 
second primary malignancies) on SAE forms will continue to be sent by the investigator to
Celgene.
Non-serious adverse events will no longer be collected on a CRF by Celgene, but should be 
recorded in the subjects’ medical records and reviewed by the study monitor.
21.1.1.
Abnormal laboratory values defined as adverse events
An abnormal laboratory value is considered to be an AE if the laboratory abnormality is
characterized by any of the following:
!
Results in discontinuation from the study.
!
Requires treatment, modification/interruption of study drug dose, or any other 
therapeutic intervention.
!
Is judged by the Investigator(s) to be of significant clinical importance.
&(/*(1(35235,(7$5<,1)250$7,21
t t 
f that 
that 
e
symptoms 
ymptoms 
AE, or abus
E, or abu
ported as a
ported as 
ould be rep
uld be
ments may i
nts may i
l symptoms
sympt
minat
minatioion fin
fi
titime of sig
me of s
designated 
designated
patient
patient’s s
s 
ours of the
ours of the
sing
sing th
the SA
e SA
l Amendm
Amend
l
on SAE for
n SAE for
ntnts will no
ill n
cts’ medica
cts’ medi
normal lab
ormal lab
al laborator
al laborato
rized by
ed by an
a
y
!
Res
Res
!

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
107
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page of the CRF. If the abnormality was not a part of 
a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
21.1.2.
Serious adverse event
A serious adverse event (SAE) is any AE which:
!
Results in death
!
Is life-threatening (i.e., in the opinion of the Investigator(s) the patient is at immediate 
risk of death from the AE)
!
Requires inpatient hospitalization or prolongation of existing hospitalization
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
patient’s ability to conduct normal life functions)
!
Is a congenital anomaly/birth defect
!
Constitutes an important medical event
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the patient or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations which: were planned before entry into the 
clinical study; are for elective treatment of a condition unrelated to the studied indication or its 
treatment; occur on an emergency outpatient basis and do not result in admission (unless 
fulfilling other criteria above); are part of the normal treatment or monitoring of the studied 
indication and are not associated with any deterioration in condition.
If an AE is considered serious, both the AE pages of the CRF and the SAE Report Form must be 
completed.
For each SAE, the Investigator(s) will provide information on severity, start and stop dates, 
relationship to study drug, action taken regarding study drug, and outcome.
Second primary malignancies will be monitored as events of interest and must be reported as 
serious adverse events regardless of the treatment arm the subject is in (see Appendix 21.1.9).  
This includes any second primary malignancy, regardless of causal relationship to study drug 
(lenalidomide or Investigator Choice arm drugs), occurring at any time for the duration of the 
study, from the time of signing the ICD through follow-up for overall survival. The Follow-Up 
Phase involves patient contact every 90 days (± 15 days) until patient death or until either 70% 
of the patients have died, or the median follow-up in responding patients is > 2 years, or the 
median duration of response (overall response and CR/CRu) has been reached, or four years 
from last patient randomized, whichever comes later. Events of second primary malignancy are 
to be reported using the SAE report form and must be considered an “Important Medical Event” 
even if no other serious criteria apply; these events must also be documented in the appropriate 
page(s) of the CRF and subject’s source documents.  Documentation on the diagnosis of the 
&(/*(1(35235,(7$5<,1)250$7,21
diate
diat
on
disrupt
disruptioion o
n
ay not be im
y not be i
may
may j
y eopa
eo
he other out
e other out
deciding wh
eciding w
tions which
ions whic
nditio
ndition un
n un
nt basis and
t basis and
f the norma
f the norma
any deterio
any deterio
th the AE p
th the AE
gator(s) wil
tor(s) wil
ug, acti
ug, a
on t
on
alignancies 
lignancies 
vents rega
vents rega
any
ny second
secon
y
ide or Inve
e or Inve
om
o
the tim
the tim
m
e invo
e involves 
lves
the pati
the patient
en
median du
median du
rom lala

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
108
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
second primary malignancy must be provided at the time of reporting as a serious adverse event 
(e.g., any confirmatory pathology results, imaging results, etc.).
21.1.3.
Classification of severity
For both AEs and SAEs, the investigator(s) must assess the severity of the event. The severity of 
AEs will be graded based upon the patient’s symptoms according to National Cancer Institute 
(NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) 
(http://ctep.cancer.gov/reporting/ctc.html). The AEs will be evaluated for severity according to 
the following scale:
Grade 1 = Mild
Grade 2 = Moderate
Grade 3 = Severe
Grade 4 = Life Threatening
Grade 5 = Death
21.1.4.
Classification of Relationship/Causality of adverse events (SAE/AE) to study 
drug
The Investigator(s) must determine the relationship between the administration of study drug and 
the occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
The temporal relationship of the adverse event to study drug 
administration makes a causal relationship unlikely or 
remote, or other medications, therapeutic interventions, or 
underlying conditions provide a sufficient explanation for the 
observed event
Suspected:
The temporal relationship of the adverse event to study drug 
administration makes a causal relationship possible, and other 
medications, therapeutic interventions, or underlying conditions 
do not provide a sufficient explanation for the observed event.
21.1.5.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
21.1.6.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(e.g., discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
&(/*(1(35235,(7$5<,1)250$7,21
events (SA
vents (SA
n the admin
the adm
ected as def
ted as d
ip of
p of
i
the ad
the a
f
s s a causal 
a causa
medicati
edication
on
ndit
nditioions pro
ns pro
entnt
mporal
pora
m
rel
re
l
ministration
inistration
medicat
medicatioion
do not pr
o no
on
on
and SAEs, 
nd SAEs
.
Actio
ctio
he Investig
he Investig
(e.g.
e. , disc
disc
ddi
ddititi
i o

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
109
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.1.7.
Outcome
All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until recovered, recovered with sequelae, not recovered (death due to another 
cause) or death (due to the SAE). 
21.1.8.
Monitoring and reporting of adverse events
All patients will be monitored for AEs during the study.  Assessments may include monitoring of 
any or all of the following parameters: the patient’s clinical symptoms; laboratory, pathological, 
radiological, or surgical findings; physical examination findings; or other appropriate tests and 
procedures.
Following the approval of Protocol Amendment #6, only serious adverse event data (including 
second primary malignancies) on SAE forms will continue to be sent by the investigator to
Celgene.
Non-serious adverse events will no longer be collected on a CRF by Celgene, but will be 
recorded in the subjects’ medical records.
21.1.9.
Immediate reporting of serious adverse events
Any AE that meets the criterion for any SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE pages of the CRF.  The Investigator(s) is required to ensure 
that the data on these forms is accurate and consistent.  This applies to all SAEs, regardless of 
relationship to study drug, that occur during the study, those made known to the Investigator(s) 
within 30 days after a patient’s last dose of study drug, any second primary malignancies 
occurring at any time for the duration of the study through follow-up for overall survival, and 
those made known to the investigator(s) at anytime that are suspected of being related to study 
drug.
The SAE must be reported immediately (i.e., within 24 hours of the Investigators’ knowledge of 
the event) to Celgene Drug Safety by facsimile.  An initial written report (prepared by the 
Investigator(s) using the SAE Report Form provided by Celgene) is to be faxed to Celgene Drug 
Safety. The immediate reporting process and timelines apply also to reporting second primary 
malignancies (see Appendix 21.1.2).
The SAE report should provide a detailed description of the SAE and include copies of hospital 
records and other relevant documents.  If a patient has died and an autopsy has been performed, 
copies of the autopsy report and death certificate are to be sent to Celgene as soon as these 
become available.  Any follow-up data will be detailed in a subsequent SAE Report Form, and 
sent to Celgene.
The Investigator(s) is responsible for informing the Institutional Review Board/Ethics 
Committee (IRB/IEC) of the SAE and providing them with all relevant initial and follow-up 
information about the event. The Investigator(s) must keep copies of all SAE information, 
including correspondence with Celgene and the IRB/IEC, on file.  All SAEs that have not 
resolved upon discontinuation of the patient’s participation in the study must be followed until 
either the event resolves completely, stabilizes/resolves with sequelae, or returns to baseline (if a 
baseline value is available).
&(/*(1(35235,(7$5<,1)250$7,21
al,l,
and 
nd 
(including
(including
tigator to
igator to
ene, but wil
ene, but wil
mpletion of 
mpletion o
he Invest
e Investigi
This applie
This appli
y, those m
, those ma
drug, 
drug, any s
ny
udy
dy th
th
y
rough
roug
h
any
nytiti
y me tha
me tha
ely
ely (i(i
y
.e., wi
.e.,
by facsimi
by facsimi
Report Form
eport Form
rting proces
rting proc
dix 21.1.2
21.1 )
ld provide 
ld provid
elevant do
elevant do
utopsy
utopsy repo
repo
y
lable.  Any
lable.  Any
elgene.
ene.
nve
nvesti
stigator
gato
ommittee (I
ommittee (I
inform
nformatatioio
ncludin
ncludi
l

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
110
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.1.10.
Pregnancies
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female patient or the female partner of a male patient occurring while the 
patient is on study drug, or within 30 days of the patient’s last dose of study drug, are considered 
immediately reportable events. Immediate is defined as within 24 hours of the study site’s 
knowledge of the event. Study drug is to be discontinued immediately and the patient instructed 
to return any unused portion of the study drug to the investigator(s).  The pregnancy, suspected 
pregnancy, or positive pregnancy test must be reported to Celgene Drug Safety immediately by 
facsimile using the SAE Report Form.
The female should be referred to an obstetrician-gynecologist experienced in reproductive 
toxicity for further evaluation and counseling.
The Investigator(s) will follow the female patient until completion of the pregnancy, and must 
notify Celgene Drug Safety of the outcome of the pregnancy as a follow-up to the initial SAE 
report. Infant follow-up will occur for one year following birth in a FCBP who was treated with 
lenalidomide.
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (i.e., 
spontaneous or therapeutic abortion [any congenital anomaly detected in an aborted fetus is to be 
documented], stillbirth, neonatal death, or congenital anomaly [including that in an aborted 
fetus]), the Investigator(s) should follow the procedures for reporting SAEs (i.e., report the event 
to Celgene Drug Safety by facsimile within 24 hours of the Investigator’s knowledge of the 
event).
In the case of a live “normal” birth, Celgene Drug Safety should be advised by facsimile within 
24 hours of the Investigator’s knowledge of the event.
All neonatal deaths that occur within 30 days of birth should be reported, without regard to 
causality, as SAEs.  In addition, any infant death after 30 days that the Investigator(s) suspects is 
related to the in utero exposure to the study drug should also be reported to Celgene Drug Safety 
by facsimile within 24 hours of the Investigators’ knowledge of the event.
If the female is found not to be pregnant, any determination regarding the patient’s continued 
participation in the study will be determined by the Investigator(s) and the Celgene Medical 
Monitor.
21.1.11.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail.  The response time is expected to be no more than five (5) business 
days.  Urgent queries (e.g., missing causality assessment) may be handled by phone.
21.1.12.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to lenalidomide based on the Investigator Brochure and for 
chlorambucil, cytarabine, rituximab, fludarabine, or gemcitabine based on the UK SPCs.
For countries within the European Union, Celgene will report in an expedited manner to 
Regulatory Agencies and Ethics Committees concerned, adverse events in accordance with the 
&(/*(1(35235,(7$5<,1)250$7,21
y
ve
ncy, and mu
ncy, and m
o the init
 the initial 
ial
who was tre
who was tr
ssificat
ificatioion
ected in an
ted in an
y [including
[includi
y
r reporting 
reporting
the Investig
he Inves
g Safet
g Safe y sh
sh
he event.
e event.
ays of birth
ays of birth
fant death a
ant death 
e study
e study dru
d
y
he Investiga
he Investig
be pregnant
be pregnan
will be dete
ll be dete
 Queries
Queries
ining to SA
ing to SA
r electronic
electroni
Urgent quer
Urgent quer
.1.12.
.12.
E
For the p
For the p
ents
ents

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
111
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Detailed Guidance on the collection, verification and presentation of adverse reaction reports 
arising from clinical trials on medicinal products for human use (ENTR/CT3) and also in 
accordance with country specific requirements.
Celgene shall notify the Investigator of the following information:
!
Any AE associated with the use of study drug in this study or in other studies that is 
both serious and unexpected, i.e., suspected unexpected serious adverse reaction 
(SUSAR). Note that such cases from blinded studies will be unblinded for reporting 
purposes.
!
Any finding from tests in laboratory animals suggests a significant risk for human 
patients including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local regulations, the Investigator shall notify his/her IRB/IEC promptly of 
these new serious and unexpected AE(s) or significant risks to study subjects.
The Investigator must keep copies of all pertinent safety information, including correspondence 
with Celgene and the IRB/IEC, on file (see Section 18.3 for records retention information).
For Local Drug Safety Affiliate Office contact information, please refer to the Serious Adverse 
Event Report Form Completion Guidelines 
ma
man n
y.y.
prompt
promptly o
ly 
ding corres
ding corres
ntion inform
ion in
efer to the 
fer to the 

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
112
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.2.
Declaration of Helsinki
Initiated: 1964 17.C
Original: English
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI
Ethical Principles for Medical Research Involving Human Subjects
Adopted by the 18th WMA General Assembly
Helsinki, Finland, June 1964 and amended by the
29th WMA General Assembly, Tokyo, Japan, October 1975
35th WMA General Assembly, Venice, Italy, October 1983
41st WMA General Assembly, Hong Kong, September 1989
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000
Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 2002
Note of Clarification on Paragraph 30 added by the EMA General Assembly, Tokyo 2004
21.2.1.
Introduction
1. The World Medical Association has developed the Declaration of Helsinki as a statement 
of ethical principles to provide guidance to physicians and other participants in medical 
research involving human patients. Medical research involving human patients includes 
research on identifiable human material or identifiable data.
2. It is the duty of the physician to promote and safeguard the health of the people. The 
physician’s knowledge and conscience are dedicated to the fulfillment of this duty.
3. The Declaration of Geneva of the World Medical Association binds the physician with
the words, "The health of my patient will be my first consideration," and the International 
Code of Medical Ethics declares that, "A physician shall act only in the patient's interest 
when providing medical care which might have the effect of weakening the physical and 
mental condition of the patient."
4. Medical progress is based on research which ultimately must rest in part on 
experimentation involving human patients.
5. In medical research on human patients, considerations related to the well being of the 
human patient should take precedence over the interests of science and society.
6. The primary purpose of medical research involving human patients is to improve 
prophylactic, diagnostic and therapeutic procedures and the understanding of the etiology 
and pathogenesis of disease. Even the best-proven prophylactic, diagnostic, and 
therapeutic methods must continuously be challenged through research for their 
effectiveness, efficiency, accessibility and quality.
7. In current medical practice and in medical research, most prophylactic, diagnostic and 
therapeutic procedures involve risks and burdens.
&(/*(1(35235,(7$5<,1)250$7,21
Africa, Oc
Africa, Oc
October 200
October 2
Assembly,
Assembl
eral Assemb
al As
d the Decla
d the Decla
physicians
physicians
ical
cal researc
resea
l
al or ident
al or ident
prom
promote and
ote an
nscience ar
nscienc
a of the Wo
a of the W
of my pat
f my patiei
hics declare
ics decla
medical car
medical c
on of
n of the p
the
f
rogress is b
rogress is b
mentation in
mentation
medical res
edical res
hu
h man 
an pat
pati
6.6. The pri
The pr
prop
prop
a

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
113
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
8. Medical research is patient to ethical standards that promote respect for all human beings 
and protect their health and rights. Some research populations are vulnerable and need 
special protection. The particular needs of the economically and medically disadvantaged 
must be recognized. Special attention is also required for those who cannot give or refuse 
consent for themselves, for those who may be patient to giving consent under duress, for 
those who will not benefit personally from the research and for those for whom the 
research is combined with care.
9. Research Investigators should be aware of the ethical, legal and regulatory requirements 
for research on human patients in their own countries as well as applicable international 
requirements. No national ethical, legal or regulatory requirement should be allowed to 
reduce or eliminate any of the protections for human patients set forth in this Declaration.
21.2.2.
Basic Principles for All Medical Research
10. It is the duty of the physician in medical research to protect the life, health, privacy, and 
dignity of the human patient.
11. Medical research involving human patients must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant 
sources of information, and on adequate laboratory and, where appropriate, animal 
experimentation.
12. Appropriate caution must be exercised in the conduct of research which may affect the 
environment, and the welfare of animals used for research must be respected.
13. The design and performance of each experimental procedure involving human patients 
should be clearly formulated in an experimental protocol. This protocol should be 
submitted for consideration, comment, guidance, and where appropriate, approval to a 
specially appointed ethical review committee, which must be independent of the 
investigator, the sponsor or any other kind of undue influence. This independent 
committee should be in conformity with the laws and regulations of the country in which 
the research experiment is performed. The committee has the right to monitor ongoing 
trials. The researcher has the obligation to provide monitoring information to the 
committee, especially any serious adverse events. The researcher should also submit to 
the committee, for review, information regarding funding, sponsors, institutional 
affiliations, other potential conflicts of interest and incentives for patients.
14. The research protocol should always contain a statement of the ethical considerations 
involved and should indicate that there is compliance with the principles enunciated in 
this Declaration.
15. Medical research involving human patients should be conducted only by scientifically 
qualified persons and under the supervision of a clinically competent medical person. The 
responsibility for the human patient must always rest with a medically qualified person 
and never rest on the patient of the research, even though the patient has given consent.
16. Every medical research project involving human patients should be preceded by careful 
assessment of predictable risks and burdens in comparison with foreseeable benefits to 
the patient or to others. This does not preclude the participation of healthy volunteers in 
medical research. The design of all studies should be publicly available.
&(/*(1(35235,(7$5<,1)250$7,21
s s 
onal
nal
wed to
ed to
eclarat
eclaratioion
healt
health, priv
h, pri
generally ac
enerally ac
ific literatu
fic literat
where app
where app
duct of res
uct of re
for researc
for researc
rimental pr
rimental p
erimental p
rimental p
nt, guidanc
nt, guidanc
w committe
w committe
y other kin
other kin
y
formit
ormity y wi
w
is performe
is performe
has the obl
has the obl
ally y any
any ser
y
for review,
for review
other poten
her poten
arch protoc
arch proto
ved and sho
ved and sho
s Declarat
Declarati
Medical r
Medical r
quali
qualififi
resp
resp

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
114
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
17. Physicians should abstain from engaging in research projects involving human patients 
unless they are confident that the risks involved have been adequately assessed and can 
be satisfactorily managed. Physicians should cease any investigation if the risks are found 
to outweigh the potential benefits or if there is conclusive proof of positive and beneficial 
results.
18. Medical research involving human patients should only be conducted if the importance of 
the objective outweighs the inherent risks and burdens to the patient. This is especially 
important when the human patients are healthy volunteers.
19. Medical research is only justified if there is a reasonable likelihood that the populations 
in which the research is carried out stand to benefit from the results of the research.
20. The patients must be volunteers and informed participants in the research project.
21. The right of research patients to safeguard their integrity must always be respected. Every 
precaution should be taken to respect the privacy of the patient, the confidentiality of the 
patient’s information and to minimize the impact of the study on the patient's physical 
and mental integrity and on the personality of the patient.
22. In any research on human beings, each potential patient must be adequately informed of 
the aims, methods, sources of funding, any possible conflicts of interest, institutional 
affiliations of the researcher, the anticipated benefits and potential risks of the study and 
the discomfort it may entail. The patient should be informed of the right to abstain from 
participation in the study or to withdraw consent to participate at any time without 
reprisal. After ensuring that the patient has understood the information, the physician 
should then obtain the patient's freely given informed consent, preferably in writing. If 
the consent cannot be obtained in writing, the non-written consent must be formally 
documented and witnessed.
23. When obtaining informed consent for the research project the physician should be 
particularly cautious if the patient is in a dependent relationship with the physician or 
may consent under duress. In that case the informed consent should be obtained by a 
well-informed physician who is not engaged in the investigation and who is completely 
independent of this relationship.
24. For a research patient who is legally incompetent, physically or mentally incapable of 
giving consent or is a legally incompetent minor, the investigator must obtain informed 
consent from the legally authorized representative in accordance with applicable law. 
These groups should not be included in research unless the research is necessary to 
promote the health of the population represented and this research cannot instead be 
performed on legally competent persons.
25. When a patient deemed legally incompetent, such as a minor child, is able to give assent 
to decisions about participation in research, the investigator must obtain that assent in 
addition to the consent of the legally authorized representative.
26. Research on individuals from whom it is not possible to obtain consent, including proxy 
or advance consent, should be done only if the physical/mental condition that prevents 
obtaining informed consent is a necessary characteristic of the research population. The 
specific reasons for involving research patients with a condition that renders them unable 
&(/*(1(35235,(7$5<,1)250$7,21
ions
ns
ch.
oject.
oject.
e respected
e respect
onfident
onfidentiaial
he
he pati
patient's'
st be adequ
st be adeq
flicts of int
flicts of int
and poten
and potenti
n
inform
informed 
ed
nt to partici
nt to partici
nderstood 
nderstood
en informe
en informe
ng, the non
ng, the non
ent for the r
nt for the
atieientnt is 
is in 
in
s. In that ca
. In that c
an who is n
an who is 
relationship
elationsh
pat
patieientn who
who
nt or i
t or i
n
s a l
s a le
om the leg
om the leg
groups shou
roups sh
mote the
ote the he
he
erform
ormed o
ed 
5.5. When a
When a
to de
to d
ad
ad
2

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
115
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
to give informed consent should be stated in the experimental protocol for consideration 
and approval of the review committee. The protocol should state that consent to remain in 
the research should be obtained as soon as possible from the individual or a legally 
authorized surrogate.
27. Both authors and publishers have ethical obligations. In publication of the results of 
research, the investigators are obliged to preserve the accuracy of the results. Negative as 
well as positive results should be published or otherwise publicly available. Sources of 
funding, institutional affiliations and any possible conflicts of interest should be declared 
in the publication. Reports of experimentation not in accordance with the principles laid 
down in this Declaration should not be accepted for publication.
21.2.3.
Additional Principles for Medical Research Combined with Medical Care
28. The physician may combine medical research with medical care, only to the extent that 
the research is justified by its potential prophylactic, diagnostic or therapeutic value. 
When medical research is combined with medical care, additional standards apply to 
protect the patients who are research patients.
29. The benefits, risks, burdens and effectiveness of a new method should be tested against 
those of the best current prophylactic, diagnostic, and therapeutic methods. This does not 
exclude the use of placebo, or no treatment, in studies where no proven prophylactic, 
diagnostic or therapeutic method exists.1
30. At the conclusion of the study, every patient entered into the study should be assured of 
access to the best-proven prophylactic, diagnostic and therapeutic methods identified by 
the study.2
31. The physician should fully inform the patient which aspects of the care are related to the 
research. The refusal of a patient to participate in a study must never interfere with the 
patient-physician relationship.
32. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic 
methods do not exist or have been ineffective, the physician, with informed consent from 
the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic 
measures, if in the physician’s judgment it offers hope of saving life, reestablishing 
health or alleviating suffering. Where possible, these measures should be made the object 
of research, designed to evaluate their safety and efficacy. In all cases, new information 
should be recorded and, where appropriate, published. The other relevant guidelines of 
this Declaration should be followed.
1 Note of clarification on paragraph 29 of the WMA Declaration of Helsinki
The WMA hereby reaffirms its position that extreme care must be taken in making use of a 
placebo-controlled trial and that in general this methodology should only be used in the absence 
of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even 
if proven therapy is available, under the following circumstances:
!
Where for compelling and scientifically sound methodological reasons its use is 
necessary to determine the efficacy or safety of a prophylactic, diagnostic or 
therapeutic method; or
&(/*(1(35235,(7$5<,1)250$7,21
ed d 
laid 
aid 
Care
Care
o the extent
 the exte
erapeutic va
erapeutic 
standards a
standards 
hod should
hod shoul
erapeut
erape ic m
s where no 
s where no
ntered into
ntered into
gnostic and
gnostic and
he pati
e patient w
ent w
to parti
to participa
cipa
nt, where p
nt, where 
have been
have been
free to use
free to us
e physician
e physic
atating suffe
ing su
designed 
designed t
e recorded 
e recorded
eclarat
claration
clarificatio
arificatio
WMA here
WMA her
&
acebo
acebo-cont
cont
of
of exist
exist
f
ing
ing
f prov
f prov

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
116
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
!
Where a prophylactic, diagnostic or therapeutic method is being investigated for a 
minor condition and the patients who receive placebo will not be subject to any 
additional risk of serious or irreversible harm. 
All other provisions of the Declaration of Helsinki must be adhered to, especially the need for 
appropriate ethical and scientific review. 6.10.2002
2 Note of clarification on paragraph 30 of the WMA Declaration of Helsinki
The WMA hereby reaffirms its position that it is necessary during the study planning process to 
identify post-trail access by study participants to prophylactic, diagnostic and therapeutic 
procedures identified as beneficial in the study or access to other appropriate care.  Post-trial 
access arrangements rot other care must be described in the study protocol so the ethical review 
committee may consider such arrangements during its review. 9.10.2004
&(/*(1(35235,(7$5<,1)250$7,21
o
rialal
al review
al review

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
117
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.3.
ECOG Performance Status Scale
Score
Description
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light housework, office work.
2
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about more than 50% of waking hours.
3
Capable of only limited self-care, confined to bed or chair more than 50% 
of waking hours.
4
Completely disabled.  Cannot carry on any self-care.  Totally confined to 
bed or chair
5
Dead
&(/*(1(35235,(7$5<,1)25
tally confin
tally confin
250$7,21
7
rk k 
7
$7
than 50%
than 50%
0$
25
1)
,1

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
118
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.4.
MCL International Prognostic Index (MIPI) score (Hoster, 2008)
Points
Age, y
ECOG
LDH ULN
WBC, 109/L
0
<50
0-1
<0.67
< 6.700
1
50-59
-
0.67 – 0.99
6.700-9.999
2
60-69
2-4
1 – 1.49
10.000 – 14.999
3
≥70
-
≥1.5
≥15.000
Low risk
0 – 3 points
Intermediate risk
4 -5 points
High risk
6 – 11 points
&(/*(1(35235,(7$5<,1)250$7,21
$

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
119
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.5.
Modified International Workshop Response Criteria (Cheson, 1999)
Modifications will be applied (Fisher, 2006; Kane, 2007) to the Cheson criteria in order to 
alleviate the increased potential for variability of results in small nodes and to account for the
common manifestation of MCL as extranodal disease, where sites of dominant extranodal 
disease (Target Lesions) can be included in the assessment of the sum of the perpendicular 
diameters of measurable lesions
Complete Response (CR):
!
Complete disappearance of all detectable clinical and radiographic evidence of disease and 
disappearance of all disease-related symptoms if present before therapy, and normalization of 
those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to 
NHL.
!
All lymph nodes and nodal masses must have regressed to normal size (& 1.5. cm in their 
greatest transverse diameter for nodes > 1.5 cm before therapy). Previously involved nodes 
that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have 
decreased to ≤1 cm in their greatest transverse diameter after treatment, or by more than 75% 
in the sum of the products of the greatest diameters (SPD).
!
The spleen, if considered to be enlarged before therapy on the basis of CT scan, must have 
regressed in size and must not be palpable on physical examination. However, no normal size 
can be specified because of the difficulties in accurately evaluating splenic and hepatic size. 
For instance, spleens thought to be of normal size may contain lymphoma, whereas an 
enlarged spleen may not necessarily reflect the presence of lymphoma but variations in 
anatomy, blood volume, the use of hematopoietic growth factors, or other causes. The 
determinations of splenic volume or splenic index by CT scan are cumbersome and not 
widely used. Any macroscopic nodules in any organs detectable on imaging technique should 
no longer be present. Similarly, other organs considered to be enlarged before therapy due to 
involvement by lymphoma, such as liver and kidneys, must have decreased in size.
!
If the bone marrow was involved by lymphoma before treatment, the infiltrate must be 
cleared on repeat bone marrow aspirate and biopsy of the same site. The sample on which 
this determination is made must be adequate (≥ 20mm biopsy length in aggregate). Flow 
cytometric, molecular, or cytogenetic studies are not considered part of routine assessment to 
document persistent disease at the present time. These studies should only be incorporated 
into trials examining important research questions.
Complete Response Unconfirmed (CRu): Those patients who fulfill the criteria for CR above
but with one or more of the following features:
!
A residual lymph node mass and extranodal target lesion greater than 1.5 cm in greatest 
transverse diameter that has regressed by more that 75% in the SPD. Individual nodes and 
extranodal target lesions that were previously confluent must have regressed by more than 
75% in their SPD compared with the size of the original mass.
!
Indeterminate bone marrow (increased number or size of aggregates without cytologic or 
architectural atypia).
and 
nd 
zatatioion of 
n of 
signable to
ignable to
.5. cm
5. cm i
m n th
n 
usly invo
sly involve
lv
eatment mu
atment
ment, or by
ment, or by
he basis o
he bas
f
xaminat
xamination
ely evaluat
ly evalu
may contai
may conta
presence o
presence o
oietic grow
oietic grow
nic index by
nic index by
s in any org
s in any org
er organs c
r organs 
as liver an
as liver 
lved 
lved by 
by lym
ly
arrow aspir
arrow aspir
made must b
de must b
lar, or cy
lar, or cytog
to
y
ent di
nt disease
seas
mining imp
mining imp
esponse Un
esponse Un
ne or more 
e or more 
residual lym
residual lym
transverse 
transverse
extrano
extrano
75%
75%

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
120
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Partial Response (PR)
!
≥50% decrease in SPD of the six largest dominant nodes or nodal masses and extranodal 
measurable target lesions (including hepatic lesions), which together with nodal lesions must 
decrease by ≥ 50% from baseline in their SPD).  These nodes or masses should be selected 
according to the following features:
!
Clearly measurable in at least two perpendicular dimensions
!
From as disparate regions of the body as possible
!
Include mediastinal and retroperitoneal areas of disease whenever these sites are involved
!
No increase in the size of other nodes, liver, or spleen
!
In addition to splenic and hepatic nodules, involvement of other organs is permitted to be 
considered measurable target lesions
!
Bone marrow assessment is irrelevant for determination of PR because it is assessable and 
not measurable disease; however, if positive, the cell type should be specified on the report, 
e.g. large-cell lymphoma or low-grade lymphoma (i.e., small, lymphocytic small cleaved or 
mixed small and large cells)
!
No new sites of disease
Stable disease (SD): Stable disease is defined as less than a PR (see above) but is not 
progressive disease or relapsed disease (see below)
Relapsed disease in CR or CRu patients
!
Appearance of any new lesions or increase by ≥ 50% in the size of previously involved sites
!
≥50% increase in greatest diameter of any previously identified node or measurable 
extranodal disease greater than 1 cm in its short axis or in the SPD of more than one mode
Progressive disease (PD) in PR patients or nonresponders
!
≥50 % increase from nadir in the SPD of any previously identified abnormal node or 
measurable nodal or extranodal disease for PRs or nonresponders
!
Unequivocal progression of extranodal lesions, non-target lesions and the spleen and/or liver
!
Appearance of any new lesion, with GD > 15mm if nodes, during or at the end of therapy
&(/*(1(35235,(7$5<,1)250$7,21
ved
mitted to be
itted to b
it is a
it is assess
ssess
specified o
pecifie
mphocy
phocytiti
y c s
c
n a PR (see
n a PR (see
e by
e by ≥ 50%
≥ 50%
any previo
any previo
m in its sho
in its sho
atients or 
ients or 
in the SPD
in the SP
tranodal dis
ranodal d
ession of ex
ession of e
any
any n
y ew le
ew le

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
121
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Table 11:
Summary of Modified Response Criteria
Response 
Category
Physical 
Examination
Lymph Nodes
Lymph Node 
Masses
Bone Marrow
Extranodal (i.e. 
spleen, liver)
CR
Normal
Normal
Normal
Normal
Normal
Cru
Normal
Normal
Normal
Indeterminate
Indeterminate
Normal
Normal
>75% decrease
Normal or 
indeterminate
>75% decrease
PR
Normal
Normal
Normal
Positive
Normal
Normal
#50% decrease
#50% decrease
Irrelevant
#50% decrease
Decrease in 
liver/spleen
#50% decrease
#50% decrease
Irrelevant
#50% decrease
Relapse/PD
Enlarging 
liver/spleen; 
new sites
New or 
increased
New or increased
Reappearance
New or 
increased
&(/*(1(35235,(7$5<,1)250$7,21
7,
$7
% decrease
% decrease
0$
#50% decr
50% dec
50
2
ance
ance
New
New
i
2
,1)2

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
122
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.6.
Cairo-Bishop Grading System for tumor lysis syndrome (TLS)
Grade
LTLS
Creatinine
Cardiac arrhythmia
Seizure
0
-
≤1.5 x ULN
None
None
I
+
1.5 x ULN
Intervention not 
indicated
None
II
+
>1.5-3.0 x ULN
Non-urgent medical 
intervention indicated
One brief generalized 
seizure; seizure (s) well 
controlled or infrequent; 
focal motor seizures not 
interfering with ADL
III
+
>3.0-6.0 x ULN
Symptomatic and 
incompletely controlled 
medically or controlled 
with device
Seizure in which 
consciousness is altered; 
poorly controlled seizure 
disorder; breakthrough 
generalized seizures 
despite medical 
intervention
IV
+
>6.0 x ULN
Life-threatening
Seizures of any kind are 
prolonged, repetitive or 
difficult to control
V
+
Death*
Death*
Death*
LTLS, local tumor lysis syndrome; ULN, upper limit of normal; ADL, activities of daily living.
* Probably or definitely attributable to clinical TLS.
&(/*(1(35235,(7$5<,1)25
e in which
e in which
sciousness 
ciousn
poorly
poorly cont
con
y
250$7,21
7
well
well
requent;
equent;
eizures not
zures not
wi
with
th
i
A
h
DL
DL
7
$7
didisorder;
sorde
gener
ner
des
d
25
<
ning
ing
$5
ath*
ath*
,(
5
mit of norma
mit of norma
TLS.
LS.

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
123
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.7.
Lenalidomide Pregnancy Prevention Plan for Subjects in Clinical
Trials
The Pregnancy Prevention Plan (PPP) applies to all subjects receiving lenalidomide within a 
clinical trial. The following PPP documents are included:
1. The Lenalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and 
Acceptable Birth Control Methods document (Section 21.8) provides the following 
information:
!
Potential risks to the fetus associated with lenalidomide exposure
!
Definition of female of childbearing potential (FCBP)/female not of childbearing 
potential (FNCBP)
!
Requirements for counseling of all subjects receiving lenalidomide about pregnancy 
precautions and the potential risks of fetal exposure to lenalidomide
!
Acceptable birth control methods for both female subjects of childbearing potential 
and male subjects receiving lenalidomide in the study
!
Pregnancy testing requirements for subjects receiving lenalidomide who are FCBP
2. The Lenalidomide Education and Counseling Guidance Document for each gender 
(female and male; Section 21.9 and Section 21.10 respectively) must be completed and 
signed by a trained counselor at the participating clinical center prior to each dispensing 
of lenalidomide. A copy of this document must be maintained in the subject’s records for 
each dispense.
3. The Lenalidomide Information Sheet (Section 21.11) will be given to each subject
receiving lenalidomide. The subject must read this document prior to starting
lenalidomide and each time the subject receives a new supply of lenalidomide.
21.8.
Lenalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines
and Acceptable Birth Control Methods
21.8.1.
Risks Associated with Pregnancy
Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic 
active substance that causes severe life-threatening birth defects. An embryofetal development 
study in animals indicates that lenalidomide produced malformations in the offspring of female 
monkeys who received the drug during pregnancy. A teratogenic effect of lenalidomide in 
humans cannot be ruled out. Therefore, a pregnancy prevention program must be followed.
21.8.1.1.
Definition of Females of Childbearing Potential
A FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a 
hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal 
(amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24
consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
&(/*(1(35235,(7$5<,1)250$7,21
earing
aring
bout pregn
bout pregn
de
de
childbearin
hildbe
lenalido
nalidomi
mi
ce Docu
ce Docume
m
respect
respectivel
ivel
g clinica
linical c
st be main
st be ma
(Section
Section 21
21
t mu
must read
st read
subject
ubjec rece
re
ks
ks of
of Feta
et
Birth
Birth Co
C
ated
at
with
wit
P
cturally rel
turally re
hat 
at causes 
causes 
s indicates
s indicat
ho
ho rece
received
ved
i
annot be ru
not be ru
8.1.1.
.1.1.
Def
De
A FCB
FCBP i
P i
hystere
ystere

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
124
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.8.1.2.
Definition of Females Not of Childbearing Potential
Females who do not meet the above definition of FCBP should be classified as FNCBP.
21.8.2.
Counseling
21.8.2.1.
Females of Childbearing Potential
For a FCBP, lenalidomide is contraindicated unless all of the following are met (ie, all FCBP 
must be counseled concerning the following risks and requirements prior to the start of 
lenalidomide):
!
She understands the potential teratogenic risk to the unborn child
!
She understands the need for effective contraception, without interruption, 28 days 
before starting lenalidomide, throughout the entire duration of lenalidomide, during 
dose interruptions and for at least 28 days after the last dose of lenalidomide
!
She understands and agrees to inform the Investigator if a change or stop of method 
of contraception is needed
!
She must be capable of complying with effective contraceptive measures
!
She is informed and understands the potential consequences of pregnancy and the 
need to notify her study doctor immediately if there is a risk of pregnancy
!
She understands the need to commence lenalidomide as soon as it is dispensed 
following a negative pregnancy test
!
She understands and accepts the need to undergo pregnancy testing based on the 
frequency outlined in this plan (Section 21.8.4) and in the Informed Consent
!
She acknowledges that she understands the hazards lenalidomide can cause to an 
unborn fetus and the necessary precautions associated with the use of lenalidomide.
The Investigator must ensure that a FCBP:
!
Complies with the conditions of the pregnancy prevention plan, including 
confirmation that she has an adequate level of understanding
!
Acknowledges the aforementioned requirements.
21.8.2.2.
Females Not of Childbearing Potential
For a FNCBP, lenalidomide is contraindicated unless all of the following are met (ie, all FNCBP 
must be counseled concerning the following risks and requirements prior to the start of 
lenalidomide):
!
She acknowledges she understands the hazards lenalidomide can cause to an unborn 
fetus and the necessary precautions associated with the use of lenalidomide.
&(/*(1(35235,(7$5<,1)250$7,21
on,
on, 28 day
28 day
omid
mide, dur
d
alid
alidomide
mide
ange or stop
nge or 
raceptive
ceptive m
sequences 
sequence
there is a ri
ere is a r
alid
alidomid
mide
d to under
to unde
ect
ectioion 21.
21.
nderstands
nderstand
ssary
ssary prec
pre
t a FCB
FCBP:
P:
e co
cond
nditi
it oi
hat she has
hat she 
edg
dges s the a
the
alales Not o
es Not o
BP, le
P, lenalid
nalid
counse
ns led c
ed
domi
mide):):
!
S

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
125
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.8.2.3.
Males
Traces of lenalidomide have been found in semen. Male subjects taking lenalidomide must meet 
the following conditions (ie, all males must be counseled concerning the following risks and 
requirements prior to the start of lenalidomide):
!
Understand the potential teratogenic risk if engaged in sexual activity with a pregnant 
female or a FCBP
!
Understand the need for the use of a condom even if he has had a vasectomy, if 
engaged in sexual activity with a pregnant female or a FCBP
!
Understand the potential teratogenic risk if the subject donates semen or sperm.
21.8.3.
Contraception
21.8.3.1.
Female Subjects of Childbearing Potential
Females of childbearing potential enrolled in this protocol must agree to use two reliable forms 
of contraception simultaneously or to practice complete abstinence (True abstinence is 
acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic 
abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal 
are not acceptable methods of contraception.) from heterosexual contact during the following 
time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) while
taking lenalidomide; 3) during dose interruptions; and 4) for at least 28 days after the last dose of 
lenalidomide.
The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method. If the below contraception methods are not appropriate for
the FCBP, she must be referred to a qualified provider of contraception methods to determine the 
medically effective contraception method appropriate to the subject. The following are examples 
of highly effective and additional effective methods of contraception:
!
Examples of highly effective methods:
∀
Intrauterine device (IUD)
∀
Hormonal (birth control pills, injections, implants, levonorgestrel-releasing 
intrauterine system [IUS], medroxyprogesterone acetate depot injections, 
ovulation inhibitory progesterone-only pills [e.g. desogestrel])
∀
Tubal ligation
∀
Partner’s vasectomy
!
Examples of additional effective methods:
∀
Male condom
∀
Diaphragm
∀
Cervical Cap
Because of the increased risk of venous thromboembolism in subjects with multiple myeloma 
taking lenalidomide and dexamethasone, combined oral contraceptive pills are not 
m.
use two rel
use two
ru
rue abstine
abstine
of th
f the sub
e su
tion
tion metho
ho
ua
ual contact
contac
efore startin
fore startin
4) for at lea
4) for at lea
inc
nclude on
ude on
l
elow contra
elow contra
ied provide
ied provide
od appropri
d approp
ect
ective
ive meth
m
ffec
ffectivive m
device (IUD
device (IU
al (b
(birt
i h co
c
terine syste
erine sys
ulation
lation inhi
inh
Tuba
Tubal liga
lig
∀
Partn
Partn
!
Exam
Exa

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
126
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
recommended. If a subject is currently using combined oral contraception the subject should 
switch to another one of the highly effective methods listed above. The risk of venous 
thromboembolism continues for 4 to 6 weeks after discontinuing combined oral contraception. 
The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone.
[Please note, the above highlighted text is applicable for protocols with dexamethasone-
containing lenalidomide regimens.]
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk 
of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics 
should be considered particularly in subjects with neutropenia.
21.8.3.2.
Male Subjects
Male subjects must practice complete abstinence (True abstinence is acceptable when this is in 
line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods 
of contraception.) or agree to use a condom during sexual contact with a pregnant female or a 
FCBP while taking lenalidomide, during dose interruptions and for at least 28 days after the last 
dose of lenalidomide, even if he has undergone a successful vasectomy.
21.8.4.
Pregnancy Testing
Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL must be 
performed for FCBP.
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least
25 mIU/mL) prior to starting lenalidomide. The first pregnancy test must be performed within 10
to 14 days prior to the start of lenalidomide and the second pregnancy test must be performed 
within 24 hours prior to the start of lenalidomide. The subject may not receive lenalidomide until 
the study doctor has verified that the results of these pregnancy tests are negative.
Females of childbearing potential with regular or no menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every 28 days while 
taking lenalidomide, at study discontinuation, and at Day 28 following the last dose of 
lenalidomide.
Females of childbearing potential with irregular menstrual cycles must agree to have pregnancy 
tests weekly for the first 28 days of study participation and then every 14 days while taking 
lenalidomide, at study discontinuation, and at Days 14 and 28 following the last dose of 
lenalidomide.
21.8.5.
Pregnancy Precautions for Lenalidomide Use
21.8.5.1.
Before Starting Lenalidomide
21.8.5.1.1. Female Subjects of Childbearing Potential
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least
25 mIU/mL) prior to starting lenalidomide. The first pregnancy test must be performed within 10
to 14 days prior to the start of lenalidomide and the second pregnancy test must be performed 
&(/*(1(35235,(7$5<,1)250$7,21
when this is
when this is
eg calendar
g calenda
ot acceptab
ot acceptab
pregnant f
pregna
least 28 da
east 28 da
omy.
omy.
nsi
nsiti ivivity of
ty o
i
negative pr
negative p
e first pregn
first preg
and the sec
and the sec
domi
mide
de. Th
Th
esults of th
esults of th
witi h regula
h regula
first 28 da
first 28 da
y didiscon
scontn inu
ing potenti
ng poten
e fir
first 28
st 28 d
at study
t study disc
disc
.
Pregn
Pregn
1.8.5.1.
1.8.5.1.
B
1.8.5.
1.8.5.

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
127
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
within 24 hours prior to the start of lenalidomide. The subject may not receive lenalidomide until 
the study doctor has verified that the results of these pregnancy tests are negative.
Females of childbearing potential must use two reliable forms of contraception simultaneously, 
or practice complete abstinence (True abstinence is acceptable when this is in line with the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, 
symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of 
contraception.) from heterosexual contact for at least 28 days before starting lenalidomide.
21.8.5.1.2. Male Subjects
Male subjects must agree to practice complete abstinence (True abstinence is acceptable when 
this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg 
calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or agree to use a condom during sexual contact with a 
pregnant female or a FCBP while taking lenalidomide, during dose interruptions and for at least
28 days after the last dose of lenalidomide, even if he has undergone a successful vasectomy.
21.8.5.2.
During and After Study Participation
21.8.5.2.1. Female Subjects
!
Females of childbearing potential with regular or no menstrual cycles must agree to 
have pregnancy tests weekly for the first 28 days of study participation and then every
!
28 days while taking lenalidomide, at study discontinuation, and at Day 28 following 
the last dose of lenalidomide.
!
Females of childbearing potential with irregular menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every
!
14 days while taking lenalidomide, at study discontinuation, and at Days 14 and 28 
following the last dose of lenalidomide.
!
At each visit, the Investigator must confirm with the FCBP that she is continuing to 
use two reliable methods of birth control if not committing to complete abstinence, or 
confirm commitment to complete abstinence.
!
If a FCBP considers the need to change or to stop a method of contraception, the
!
Investigator must be notified immediately.
!
Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days.
!
If pregnancy or a positive pregnancy test does occur in a subject, lenalidomide must 
be immediately discontinued.
!
Pregnancy testing and counseling must be performed if a subject misses her period or 
if her pregnancy test or her menstrual bleeding is abnormal. Lenalidomide must be 
discontinued during this evaluation.
&(/*(1(35235,(7$5<,1)250$7,21
when 
when 
[eg
[eg
e not 
not 
ontact with
ontact w
ions and fo
ions and f
ccessful vas
cessful va
or no
no me
mens
n
days
ys of
of stu
stu
ud
udy di
y discont
scon
i
l with i
with irreg
rreg
i
first 28 da
first 28 da
ididomi
mide, a
de
i
of l
of lenalid
enali
l
nvestigator
nvestigato
methods o
methods 
mi
miti ment to
ment 
BP consider
consider
stigator
igator m
Counseling
Counselin
must be
ust b
m
!
If p
If p
b

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
128
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
!
Females must agree to abstain from breastfeeding while taking lenalidomide and for 
at least 28 days after the last dose of lenalidomide.
21.8.5.2.2. Male Subjects
!
Must practice complete abstinence (True abstinence is acceptable when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or use a condom during sexual contact with a 
pregnant female or a FCBP while taking lenalidomide, during dose interruptions and 
for at least 28 days after the last dose of lenalidomide, even if he has undergone a 
successful vasectomy.
!
Must not donate semen or sperm while receiving lenalidomide, during dose 
interruptions or for at least 28 days after the last dose of lenalidomide.
!
Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days.
!
If pregnancy or a positive pregnancy test does occur in the partner of a male subject 
while taking lenalidomide, the Investigator must be notified immediately.
21.8.5.3.
Additional Precautions
!
Subjects should be instructed to never give lenalidomide to another person.
!
Subjects should be instructed to return any unused capsules to the study doctor.
!
Subjects should not donate blood while receiving lenalidomide, during dose 
interruptions and for at least 28 days after the last dose of lenalidomide.
!
No more than a 28-day lenalidomide supply may be dispensed with each cycle of 
lenalidomide.
&(/*(1(35235,(7$5<,1)250$7,21
and 
and 
ne a
e a
dose
dose
de.e.
of fetal
of fetal ex
ex
l
he partner o
he partne
otified imm
otified imm
lenalidomi
lenalidomi
any
any unused
unused
y
while receiv
while receiv
day
days after t
s after t
ido
domide su
mide s

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
129
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.9.
Lenalidomide Education and Counseling Guidance Document for
Female Subjects
To be completed prior to each dispensing of lenalidomide.
Protocol Number: 
Patient Name (Print): __________________ DOB: _____/_____/_____ (dd/mmm/yyyy)
Check one risk category:
 FCBP (Female of childbearing potential): a female who: 1) has achieved menarche 
(first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the 
surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of 
both ovaries) or 3) has not been naturally postmenopausal (amenorrhea following 
cancer therapy does not rule out childbearing potential) for at least 24 consecutive 
months (ie, has had menses at any time during the preceding 24 consecutive months)
 NOT FCBP
21.9.1.
Female of Childbearing Potential:
1. I have verified and counseled the subject regarding the following:
 Potential risk of fetal exposure to lenalidomide: A teratogenic potential of 
lenalidomide in humans cannot be ruled out. If lenalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. Females are 
advised to avoid pregnancy while taking lenalidomide. Females of childbearing 
potential must agree not to become pregnant while taking lenalidomide.
 That the required pregnancy tests performed are negative.
 The subject confirmed that she is using TWO reliable methods of birth control at the 
same time, or complete abstinence (True abstinence is acceptable when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) from heterosexual contact (at least 28 days 
prior to receiving lenalidomide, while receiving lenalidomide, during dose 
interruptions and for at least 28 days after the last dose of lenalidomide).
 One highly effective method and one additional method of birth control 
must be used AT THE SAME TIME. The following are examples of 
highly effective and additional effective methods of contraception:
!
Examples of highly effective methods:
∀
Intrauterine device (IUD)
∀
Hormonal (birth control pills, injections, implants, levonorgestrel-releasing 
intrauterine system [IUS], medroxyprogesterone acetate depot injections, 
ovulation inhibitory progesterone-only pills [e.g. desogestrel])
∀
Tubal ligation
&(/*(1(35235,(7$5<,1)250$7,21
narche
rche
y (the
(the
y
removal
moval of
o
hea f
hea fof llllol w
st 24 conse
st 24 cons
24 consecu
cons
t
the followin
he followi
ide: A terat
ide: A tera
out. If lenal
ut. If len
or death to 
or death to
aking lenal
aking lenal
me pregnan
me pregnan
tests perfo
tests perf
hat she is u
at she is u
ete abstinen
ete abstinen
and usual l
and usual 
ptothermal 
othermal
methods of 
ethods of
eceiving len
ceiving le
upti
ptions and 
ons and
One highly
ne highly
must be u
must be u
highly
highly
!

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
130
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
∀
Partner’s vasectomy
!
Examples of additional effective methods:
∀
Male condom
∀
Diaphragm
∀
Cervical Cap
 The subject confirmed that even if she has amenorrhea she must comply 
with advice on contraception.
 Pregnancy tests before, during administration of lenalidomide and at the 
last dose of lenalidomide, even if the subject agrees not to have 
reproductive heterosexual contact.
 Frequency of pregnancy tests to be done:
!
Two pregnancy tests will be performed prior to receiving lenalidomide, one 
within 10 to 14 days, and a second within 24 hours of the start of lenalidomide.
!
Every week during the first 28 days of this study and a pregnancy test every 28 
days while the subject is taking lenalidomide if menstrual cycles are regular.
!
Every week during the first 28 days of this study and a pregnancy test every 14 
days while the subject is taking lenalidomide if menstrual cycles are irregular.
!
If the subject missed a period or has unusual menstrual bleeding.
!
When the subject is discontinued from the study and at Day 28 after the last
dose of lenalidomide if menstrual cycles are regular. If menstrual cycles are 
irregular, pregnancy tests will be done at discontinuation from the study and at
Days 14 and 28 after the last dose of lenalidomide.
 The subject confirmed that she will stop taking lenalidomide 
immediately in the event of becoming pregnant and to call her study 
doctor as soon as possible.
 The subject confirmed that she has not and will not breastfeed a baby 
while taking lenalidomide and for at least 28 days after the last dose of 
lenalidomide.
 The subject has not and will never share lenalidomide with anyone else.
 The subject has not and will not donate blood while taking lenalidomide, 
during dose interruptions and for at least 28 days after the last dose of 
lenalidomide.
 The subject has not and will not break, chew, or open lenalidomide 
capsules at any point.
 The subject confirmed that she will return unused lenalidomide capsules 
to the study doctor.
2. I have provided the Lenalidomide Information Sheet to the subject.
&(/*(1(35235,(7$5<,1)250$7,21
g lenalido
enalidom
th
the start of
start o
and a pregn
nd a preg
f menstrual
f menstrual
s study
study and 
an
y
mid
mide if me
e if m
s unusual m
s unusual
ed fro
from th
t
nstrual cycle
strual cycl
s will be do
s will be do
he las
last dos
t do
d that she w
hat she w
event of be
event of be
s possible.
s possible.
confirmed 
confirm
ing lenalido
ing lenalid
omide.
mide.
e subject h
e subject
The subj
The subj
during
durin
len
le


Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
131
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.9.2.
Female Not of Childbearing Potential (Natural Menopause for at Least 24 
Consecutive Months, a Hysterectomy, or Bilateral Oophorectomy):
1. I have verified and counseled the subject regarding the following:
 Potential risk of fetal exposure to lenalidomide: A teratogenic potential of 
lenalidomide in humans cannot be ruled out. If lenalidomide is taken 
during pregnancy, it may cause birth defects or death to any unborn baby.
 The subject has not and will never share lenalidomide with anyone else.
 The subject has not and will not donate blood while taking lenalidomide, 
during dose interruptions and for at least 28 days after the last dose of 
lenalidomide.
 The subject has not and will not break, chew, or open lenalidomide 
capsules at any point.
 The subject confirmed that she will return unused lenalidomide capsules 
to the study doctor.
2. I have provided the Lenalidomide Information Sheet to the subject.
DoNotDispenseLenalidomideif:
!
The subject is pregnant.
!
No pregnancy tests were conducted for a FCBP.
!
The subject states she did not use TWO reliable methods of birth control (unless 
practicing complete abstinence from heterosexual contact) at least 28 days prior 
to receiving lenalidomide, while receiving lenalidomide and during dose 
interruptions.
!
The subject stated that she has or does not want to adhere to pregnancy 
precautions outlined within this PPP.
Counselor Name (Print):
Counselor Signature: 
Date: ___ / ___ / ___ (dd/mmm/yyyy)
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s 
records.**
&(/*(1(35235,(7$5<,1)250$7,21
e capsules
 capsules
subjec
subject.
a FCBP.
FCBP.
WO
WO reliabl
reliabl
om heteros
hetero
e receiving
e receiving
she has
he has or 
within t
within thi
h
3
ure:
re:
1
in a copy
a copy o
y
.**
*

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
132
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.10.
Lenalidomide Education and Counseling Guidance Document for
Male Subjects
To be completed prior to each dispensing of lenalidomide.
Protocol Number: 
Subject Name (Print): __________________ DOB: _____/_____/_____ (dd/mmm/yyyy)
1. I have verified and counseled the subject regarding the following:
 Potential risk of fetal exposure to lenalidomide: A teratogenic potential of 
lenalidomide in humans cannot be ruled out. If lenalidomide is taken 
during pregnancy, it may cause birth defects or death to any unborn baby.
 The subject confirmed that he has practiced complete abstinence (True 
abstinence is acceptable when this is in line with the preferred and usual 
lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, 
symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or used a condom when engaging in 
sexual contact (including those who have had a vasectomy) with a 
pregnant female or FCBP, while taking lenalidomide, during dose 
interruptions and for at least 28 days after the last dose of lenalidomide.
 The subject confirmed that he has not impregnated his female partner 
while in the study.
 The subject confirmed that he will notify his study doctor if his female 
partner becomes pregnant and the female partner of a male subject taking 
lenalidomide confirmed that she will call her healthcare provider 
immediately if she becomes pregnant.
 The subject has not and will never share lenalidomide with anyone else.
 The subject confirmed that he has not donated and will not donate semen 
or sperm while taking lenalidomide or during dose interruptions and that 
he will not donate semen or sperm for at least 28 days after the last dose 
of lenalidomide.
 The subject has not and will not donate blood while taking lenalidomide, 
during dose interruptions and for at least 28 days after the last dose of 
lenalidomide.
 The subject has not and will not break, chew, or open lenalidomide 
capsules at any point.
 The subject confirmed that he will return unused lenalidomide capsules to the study 
doctor.
2. I have provided the Lenalidomide Information Sheet to the subject.
&(/*(1(35235,(7$5<,1)250$7,21
f
n baby
n baby.
ce (True
ce (True
red and usu
ed and us
ovulat
vulatioion
awal are n
wal are n
ndo
ndom when
wh
vasectomy
asectom
idomide, du
mide, 
the l
the ast do
ast do
impregnate
impregnat
will notify 
will notify 
nd the fem
d the fem
that she wil
hat she w
omes preg
mes pre
ot and will 
ot and will 
onfirmed th
onfirme
while taking
hile taking
not donate 
not donate 
alido
alidomide
mide
The subject 
The subject
during do
during do
lenalid
enalid
 Th
Th

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
133
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
DoNotDispenseLenalidomideif:
!
The subject stated that he has or does not want to adhere to pregnancy 
precautions outlined within this PPP.
Counselor Name (Print):
Counselor Signature: 
Date: ___ / ___ / ___ (dd/mmm/yyyy)
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s 
records.**
&(/*(1(35235,(7$5<,1)250$7,21
)
ect’s
ect’s

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
134
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.11.
Lenalidomide Information Sheet
For subjects enrolled in clinical research studies
Please read this Lenalidomide Information Sheet before you start taking lenalidomide and each 
time you get a new supply. This Lenalidomide Information Sheet does not take the place of an 
informed consent to participate in clinical research or talking to your study doctor or healthcare 
provider about your medical condition or your treatment.
What is the most important information I should know about lenalidomide?
1. Lenalidomide may cause birth defects (deformed babies) or death of an unborn 
baby. Lenalidomide is similar to the medicine thalidomide. It is known that thalidomide 
causes life-threatening birth defects.
If you are a female who is able to become pregnant:
!
Do not take lenalidomide if you are pregnant or plan to become pregnant
!
You must practice complete abstinence from sexual contact with a male or use 
two reliable, separate forms of effective birth control at the same time:
∀
for 28 days before starting lenalidomide
∀
while taking lenalidomide
∀
during breaks (dose interruptions) of lenalidomide
∀
for at least 28 days after the last dose of lenalidomide
!
You must have pregnancy testing done at the following times:
∀
within 10 to 14 days prior to the first dose of lenalidomide
∀
24 hours prior to the first dose of lenalidomide
∀
weekly for the first 28 days
∀
if you have regular menstrual periods: every 28 days after the first month
∀
if you have irregular menstrual periods: every 14 days after the first month
∀
if you miss your period or have unusual menstrual bleeding
∀
28 days after the last dose of lenalidomide (14 and 28 days after the last dose if 
menstrual periods are irregular)
!
Stop taking lenalidomide if you become pregnant while taking lenalidomide
∀
If you suspect you are pregnant at any time during the study, you must stop 
lenalidomide immediately and immediately inform your study doctor. Your study 
doctor will report all cases of pregnancy to Celgene Corporation.
!
Do not breastfeed while taking lenalidomide and for at least 28 days after the 
last dose of lenalidomide
&(/*(1(35235,(7$5<,1)250$7,21
nborn 
born 
thalido
thalidomid
mi
ecome pre
come p
ontact wit
ntact wit
rol at the s
l at the 
lenalido
nalidomi
m
dos
dose of le
e of len
ing done a
ng done 
or to the fir
r to the fi
first
fir
dose
dose
first 28 da
first 28 day
regu
gular
lar m
hav
ave i
e irregu
rre
i
you
you mis
miss y
s y
28 days
28 days
menstr
menst
!
Stop
top
∀

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
135
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
∀
The study doctor will be able to advise you where to get additional advice on 
contraception.
If you are a female not able to become pregnant:
In order to ensure that an unborn baby is not exposed to lenalidomide, your study doctor 
will confirm that you are not able to become pregnant.
If you are a male:
A small amount of lenalidomide is found in human semen. The risk to an unborn baby in 
females whose male partner is receiving lenalidomide is unknown at this time.
!
Male subjects (including those who have had a vasectomy) must practice complete 
abstinence or must use a condom during sexual contact with a pregnant female or a 
female that can become pregnant:
∀
While you are taking lenalidomide
∀
During breaks (dose interruptions) of lenalidomide
∀
For at least 28 days after the last dose of lenalidomide
!
Male subjects should not donate sperm or semen while taking lenalidomide, 
during breaks (dose interruptions) and for at least 28 days after the last dose of 
lenalidomide.
!
If you suspect that your partner is pregnant any time during the study, you must 
immediately inform your study doctor. The study doctor will report all cases of 
pregnancy to Celgene Corporation. Your partner should call their healthcare 
provider immediately if they become pregnant.
2. All subjects:
!
Do not share lenalidomide with other people. It must be kept out of the reach of 
children and should never be given to any other person.
!
Do not donate blood while you take lenalidomide, during breaks (dose interruptions)
and for at least 28 days after the last dose of lenalidomide.
!
Do not break, chew, or open lenalidomide capsules at any point.
!
You will get no more than a 28-day supply of lenalidomide at one time.
!
Return unused lenalidomide capsules to your study doctor.
Additional information is provided in the informed consent form and you can ask your 
study doctor for more information.
&(/*(1(35235,(7$5<,1)250$7,21
in n
omp
mplete
lete
female or a
female or 
e
whil
while taki
28 days
28 days afa
nant any t
nant any t
r.r. Th
The stu
stu
n. You
Your pa
p
com
come preg
preg
de
de with ot
with 
never be g
never be 
oo
ood whil
while
28 da
8 days
y af
eak, chew,
eak, chew
will get no m
will get no m
eturn unuse
rn unuse
u
dditio
ti
i
na
nal ini
stud
stu y doc
doc

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
136
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
21.12.
EORTC QLQ-C30 Questionnaire
EORTC QLQ-C30 (version 3)
We are interested in some things about you and your health. Please answer all of the 
questions yourself by circling the number that best applies to you. There are no "right" or 
"wrong" answers. The information that you provide will remain strictly confidential.
Please fill in your initials:
Your birthdate (Day, Month, Year):
Today's date (Day, Month, Year):
Not at
All
A
Little
Quite
a Bit
Very
Much
1.
Do you have any trouble doing strenuous activities, 
like carrying a heavy shopping bag or a suitcase?
1
2
3
4
2.
Do you have any trouble taking a long walk?
1
2
3
4
3.
Do you have any trouble taking a short walk outside of 
the house?
1
2
3
4
4.
Do you need to stay in bed or a chair during the day?
1
2
3
4
5.
Do you need help with eating, dressing, washing 
yourself or using the toilet?
1
2
3
4
&(/*(1(35235,(7$5<,1)250$7,21
or
Not at
Not at
All
All
ies,
ies,
ase?
ase?
g walk?
walk?
3
ng a a shortrt wa
52
y in bed or a
y in bed o
d help with e
d help with 
or using the
or using the

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
137
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
During the past week:
Not at
All
A
Little
Quite
a Bit
Very
Much
6.
Were you limited in doing either your work or 
other daily activities?
1
2
3
4
7.
Were you limited in pursuing your hobbies or 
other leisure time activities?
1
2
3
4
8.
Were you short of breath?
1
2
3
4
9.
Have you had pain?
1
2
3
4
10.
Did you need to rest?
1
2
3
4
11.
Have you had trouble sleeping?
1
2
3
4
12.
Have you felt weak?
1
2
3
4
13.
Have you lacked appetite?
1
2
3
4
14.
Have you felt nauseated?
1
2
3
4
15.
Have you vomited?
1
2
3
4
16.
Have you been constipated?
1
2
3
4
17.
Have you had diarrhea?
1
2
3
4
18.
Were you tired?
1
2
3
4
19.
Did pain interfere with your daily activities?
1
2
3
4
20.
Have you had difficulty in concentrating on things, 
like reading a newspaper or watching television?
1
2
3
4
&(/*(1(35235,(7$5<,1)250$7,21
4
4
3
2
3
2
2
1
ted?
ed?
hea?
hea?
red?
ed?
pain interfe
pain interfere
Have you
Have yo
like re
like re

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
138
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
During the past week:
Not at
All
A
Little
Quite
a Bit
Very
Much
21.
Did you feel tense?
1
2
3
4
22.
Did you worry?
1
2
3
4
23.
Did you feel irritable?
1
2
3
4
24.
Did you feel depressed?
1
2
3
4
25.
Have you had difficulty remembering things?
1
2
3
4
26.
Has your physical condition or medical treatment 
interfered with your family life?
1
2
3
4
27.
Has your physical condition or medical treatment 
interfered with your social activities?
1
2
3
4
28.
Has your physical condition or medical treatment 
caused you financial difficulties?
1
2
3
4
For the following questions please circle the number between 1 and 7 that 
best applies to you
29.
How would you rate your overall health during the past week?
1
2
3
4
5
6
7
Very poor
Excellent
30.
How would you rate your overall quality of life during the past week?
1
2
3
4
5
6
7
Very poor
Excellent
©
Copyright 1995 EORTC Quality of Life Group. All rights reserved. Version 3.0
&(/*(1(35235,(7$5<,1)250$7,21
4
4
3
2
1
e circle th
e circle th
overall
overa
he
h
2
3
ululd y
d you rat
ou ra
ery poor
poor
y
©
Copyrig
opyrig

Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
8VHU1DPH
7LWOH
'DWH7KXUVGD\0D\30(DVWHUQ'D\OLJKW7LPH
0HDQLQJ$SSURYHGQRFKDQJHVQHFHVVDU\
                                                
&(/*(1(35235,(7$5<,1)250$7,21

Lenalidomide CC-5013
Summary of Changes CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
3
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
1.
JUSTIFICATION FOR AMENDMENT
This protocol is being amended to address the study treatment needs of subjects in countries 
where subjects can only receive lenalidomide treatment under a clinical trial protocol as post-
trial access following the final lock of the clinical trial database.
Following approval of Amendment 6 and the closure of the clinical database, only serious 
adverse events and drug administration data will be collected by Celgene. 
Amendment 6 will apply to 2 ongoing study subjects in Russia.
Significant changes included in this amendment are summarized below:
!
Study Treatment Allocation Procedure (IMS Drug Ordering System (IDOS) will replace 
Interactive Voice Recognition System (IVRS)), and removal of all Central Laboratory 
Contacts.
Updated section: Section 1
!
Extended Access Phase added
Updated sections: Synopsis, Table 2 footnotes, Table 3 footnotes, new Table 4, Section 8.1, 
Section 8.1.2.2, Section 8.2, Figure 1 footnote, Section 11.9, Section 11.11, Section 12.2, 
Section 13.3, Section 15, Section 16.3, Section 18.2.
!
Case report form (CRF) pages no longer need to be completed following closure of the 
clinical database
Updated sections: Synopsis, new Table 4, Section 8.1, Section 10.1.7, Section 10.1.8, Section 
10.2, Section 11.9, Section 11.11, Section 11.6, Section 13.3, Section 16.3, Section 18.2, 
Appendix 21.1, Appendix 21.1.8.
!
Added Table 4 Schedule of Study Assessment: Guidance for Extended Access Phase
!
Clarified collection of overall survival data
Updated sections; Synopsis, Table 2 footnotes, Table 3 footnotes, Section 8.1, Section 
8.1.2.2, Section 12.2.
!
Reporting of serious adverse events (SAEs) (including [second primary 
malignancies]SPMs) information to Celgene
Updated sections: Synopsis, new Table 4, Section 8.1, Section 8.1.2.2, Section 8.2, Section 
12.2, Section 13.3, Appendix 21.1, Appendix 21.1.8.
!
Included the statement in the case of pregnancies “Infant follow-up will occur for one 
year following birth in a FCBP who was treated with lenalidomide.”
Section 21.1.10
!
Clarified collection of drug accountability information.
Updated sections: Synopsis, new Table 4, Section 8.1, Section 8.1.2.2, Section 10.1.8, 
Section 10.2, Section 11.9, Section 11.11, Section 12.2, Section 16.3, Section 18.2.
!
Closure of study Follow-up phase
&(/*(1(35235,(7$5<,1)250$7,21
illll repla
replace
ce
aboratory
aboratory
s, new 
new Tab
Tab
Section 11
ection 1
e com
e complete
plete
m
on 8.1, 
on 8.1, Sec
e
1.6, Section
1.6, Secti
y A
y
ssessme
ssess
l survival d
surviva
l
Table 2 fo
Table 2 fo
ous adverse
ous adve
SPMs) info
SPMs) in
ons: Synop
ons: Synop
on 13.3
on 13.3, Ap
, A
luded the s
uded the s
year fo
year follo
llow
Secti
Section 21
on 21
!
Cl
Cl
Up
U

Lenalidomide CC-5013
Summary of Changes CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
4
CC-5013-MCL-002 Amendment #6 Final: 31 May 2018
Updated sections: Synopsis, Table 2 footnotes, Table 3 footnotes, Section 8.1.2.2, Section 
12.2.
!
Access to lenalidomide in the commercial setting and ending of the study.
Updated sections: Synopsis, Table 2 footnotes, Table 3 footnotes, Section 8.1, Section 
8.1.2.2, Section 13.3.
!
Update of the Lenalidomide Pregnancy Prevention Program in Clinical Trials
Updated Sections: new Appendix 21.7, new Appendix 21.8, new Appendix 21.9, Section 
21.10, Section 21.11.
The amendment also includes other clarifications and corrections:
!
Coordinating Principal Investigator role discontinued
!
Change to Safety Contact Information for non European Union (EU) countries
!
Change to the Medical Monitor and Study Manager
Updated Section: Section 1
&(/*(1(35235,(7$5<,1)250$7,21
ountries
untries

Lenalidomide (CC-5013)
Summary of Changes CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
3           CC-5013-MCL-002  Amend #5 final: 22 Mar 2013
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:
!
The amendment updates the study team contact information due to changes in personnel. 
∀
This is noted in Protocol section 1 (Table 1; and Name of central laboratory(ies) and 
other medical and/or technical department(s) and/or institutions).
!
The amendment modifies the requirement for thromboembolic prophylaxis (Synopsis: 
Thromboembolism; and Protocol section 10.1.6). 
∀
This modification was implemented following a DMC recommendation for 
implementing mandatory prophylaxis for all study patients on lenalidomide after the 
DMC observed an increase in thromboembolic events in the lenalidomide arm 
compared to the control arm, and that a number of the patients with thromboembolic 
events were not receiving anti-thromboembolic prophylaxis.
&(/*(1(35235,(7$5<,1)250$7,21
:
de after the
de after th
mide arm
mide arm
thromboe
thrombo

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
3
CC-5013-MCL-002 Amend #4 Final:  27 Sep 2011
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:
!
The amendment updates the Global Drug Safety address due to relocation. 
∀
This is noted in Protocol section 1: Table 1.
!
 
 
 
!
The amendment adds MIPI score at randomization to the list of treatment and clinical 
characteristics at screening/baseline, also to be analyzed as a stratification factor, and
also to the list for subgroup analysis in the Synopsis (Study design and Efficacy Analysis) 
and in Protocol sections 8.1.2.1 and 15.1.6).
∀
This addition was implemented following recommendation from the third DMC for 
analysis according to MIPI at randomization, after the DMC observed an imbalance in 
terms of risk factors between the study arms which was not mitigated by the 
stratification factors.
!
The amendment adds a fourth safety analysis to occur after 200 patients complete 2 cycles 
or withdraw before completing 2 cycles (Synopsis: Data Monitoring Committee; and 
Protocol sections 8.3 and 15.7).
∀
This addition was implemented to ensure ongoing safety monitoring with sample size 
increase to 250 pts.
!
The amendment increases the sample size to 250 patients (Synopsis: Number of patients; 
Protocol: Figure 1).
∀
This sample size increase was implemented following recommendation from the third 
DMC to allow a more reliable estimation of potential PFS differences between the 
study arms after the DMC observed that the outcome in the control arm of the study 
was different from the initial assumptions used to calculate the sample size.
!
The amendment modifies the duration of prior malignancy-free history (Synopsis: 
Exclusion Criteria; and Protocol section 9.2).
∀
This modification was implemented as requested by health authorities to reduce the 
risk of second primary malignancy (SPM) in patients treated with lenalidomide.
!
The amendment updates the safety wording on second primary malignancies in the 
Synopsis (Safety, footnote 15 to Table 2, footnote 7 to Table 3) and Protocol sections 8.2, 
13.1 and 21.1.2.
∀
This is the current SPM language according to the updated protocol template safety 
wording.
&(/*(1(35235,(7$5<,1)250$7,21
ent and clin
nt and cli
cation fact
cation fact
n and Effic
and Ef
ation from
he DMC o
he DMC
ch was not 
h was no
toto occur af
occur 
nopsis: Da
nopsis: Da
to ensure o
to ensure 
e sample s
e sample s
increase
ncrease w
a more re
a more r
after the D
after the 
erent fro
erent from
ndment 
dmen mo
m
sion Criter
ion Criter
This m
his m
ririsk 
sk 
!
The a
The a
Syn
Sy
$7
0$
50$

Lenalidomide (CC-5013)
Protocol: CC-5013-MCL-002
Celgene Corporation
Confidential and Proprietary
4
CC-5013-MCL-002 Amend #4 Final:  27 Sep 2011
!
The amendment increases the sample size to 250 patients and modifies the Efficacy 
analysis (Synopsis: Statistical Analysis; and Protocol sections 15.2.1, 15.2.3, 15.7, and 
15.8 ).
These changes were implemented following recommendations from the third study DMC: 
∀
To allow a more reliable estimation of potential PFS differences between the study 
arms after the DMC observed that the outcome in the control arm of the study was 
different from the initial assumptions used to calculate the sample size; 
∀
Sub-populations and sub-groups are added to the analyses to evaluate potential 
correlation between safety and efficacy outcomes based on baseline characteristics or 
response to treatment in different patient populations; and 
∀
For analysis according to MIPI at randomization after the DMC observed an 
imbalance in risk factors between the study arms which was not mitigated by the 
stratification factors.
!
The amendment adds sub-populations and sub-groups to the study analyses (Synopsis: 
Table 4; and Protocol sections 15.1and 15.9).
∀
Sub-populations and sub-groups are added to the analyses to evaluate potential 
correlation between safety and efficacy outcomes based on baseline characteristics or 
response to treatment in different patient populations.
!
The amendment further clarifies and aligns the follow-up requirements for second 
primary malignancies in the Synopsis (Cross over) and Protocol sections 8.1.2.3 and 
8.1.2.4.
∀
Further clarification and protocol wording alignment of the SPM follow-up 
requirements.
!
The amendment adds a fourth EORTC QoL compliance assessment to occur after 200 
patients complete 2 cycles or withdraw before completing 2 cycles (Protocol section 
15.2.2).
∀
This addition was implemented to ensure ongoing monitoring of EORTC QoL 
compliance with sample size increase to 250 pts.
!
The amendment updates the safety language according to the updated protocol template 
safety wording in Protocol section 21.1.
&(/*(1(35235,(7$5<,1)250$7,21
tics or 
ics or 
ed an
d an 
gated by
gated by th
y
dy analyses
analys
yses to eval
yses to eva
ased on
ased on ba
b
ions.
ons.
follow
follow-up r
up
over) and 
over) and P
wording
wording alal
EORTC Qo
EORTC 
withdraw 
withdraw
s impleme
mpleme
ith
th
i
sample
sampl
h
nt update
updates
e
ing 
ing in
in Prot
Pro

      
          
      
     

        !" #   
$
C    
+ + +         5 , 3"

  !! ! !   
#

$       +  +    $, 6  (    + ,     
   + /  ++    /   4

  !!      % !  
 !          
   #

$ +  33    +      $  1 7  3
      +  +  -4441 -444.1 41  44 $   
+      +        1 $  1 
7  3 1        $,  8 1     +  +  -4441 
-444.1 
1 4-41  4-44

  !! % !  !!   
'       !  !   
!!()  * #  *
+&   ,-(./0)    
  1-2     ! *    34
 !  (5"5)  
 ! ! 6   !#

&+  2 ,     +     +  ++  
3   4      + 3    +  9   +  
   +1    9   ,:+        , 
  3   +          +     +   ++4 

'             2  +     +   ++ 
 ,:+ +2    + 1    +   ,     ; 
 +     +    2  2     
  2 2        <           
'      ! +   ' !     3    2 224 $ 7  3
=  2 2  + + 2 #   >         
 ?@     2 1        3      
A  1              2     &/ &  , 
+1             51 3+2 +   4 

$      +        1 $  1 
7  3 1    1  1 $,  8    1 $,  8 
   1 $, . ,  '      ! +   ' !1     +  
+  -4441 -444.1 -41 41 41 4B1 441  44B4
&(/*(1(35235,(7$5<,1)250$7,21


 

 1 7 
 1 
$  
$  
 1 $ 
 1 $ 
 +  + 
+  + 
! 
!
 !
 !


(./0)
(./0)
 
 
(

! 6
! 6
   + 
   + 
+ 3
+ 3
  9
  
   
  
   
  
2 
2  

   
   
2 2
 2
   
   
 2 
 2 
 ?@  
 ?@  
A  
 

+
+

$
$

      
          
      
     
.
        !" #   

  !!       
 ( ' 7& ! 8  '  
  9 & :#/;#/#4,#/)

$  3  +  3   +        3   
+         2   +1 3+     4

  !!      !  
!  ( ' 7'  !
  9 & 1#4;#//4#4/0#4#44/#0)#

$  3  +           +  
'  C 9  &     'C& 

  !!  !!!  *
  ( ' 7*9  <9 /9
& ;#/#4#<)#

$ ++  +     +   2   +      
       +         +  2  6 

   ++  +   ,        + 
     $,     +  ! 4

  !!    ! % ! *  4;
 ( ' 7* 9& ;#/#4#=)#

$ ++    5      ;        
   3 2 -              +  2 
 4 

  !!        '!! &
      >   !    ?  
 (    )?     
( ' 7'' 9& /-#/#4)#

  !!  !     *? 
! ! 9    *?   9
  !          
       !
    ( ' *   9& /0#4#<)#

$   9  3 ,        9   ++   
+  +     , +++ +   +  4
&(/*(1(35235,(7$5<,1)250$7,21
  
  
 /9
 /9
+  
+ 
  + 
 + 
    
    
 

 9
 9
  
 
   
   
     
   
>  
> 
 
 
'
'
 
 
  
  
!
!
 
 
 
 
 

+
+

      
          
      
     

        !" #   

  !!      !        
  !     @!! %  
 @ ( ' *   9& /0#1)#

  !!   % !  !   ! *
!(  4<9& /-#/#//-#/#<)#

$ ++  +      1      ?      
   ,   + 3   ++1        , 
       3 > 2 3 34

  !! !      ! (  
:  ;)#

 +  ;            D   ;   
+  4 

$   2      +     2     +  4 
$    ,  3   ,        2     3+    
     +     3   +     +4 

  !!  % ! "! !   !
       (& /-#/#1/-#/#;)#

$ ;     /+ +    +        + +   
+            +  + 4

$ ;         ,          
      + 4


 

  !!       ! 
$        
(&' /0#/#=)#

  !!    ( ' 7
B? 9& 0#/0#4#4/-#/#04-)#

$ ,+       +  F      &+ +  
 2   6 3  ,+  +        
2  ++  <   &+ +    ,+   3 2,6 
3  3 ,+  +         2  ++  
<    &+ +   D2 D4 1 75 G4 6 2 + +     
 +     9        4 
&(/*(1(3
  
  


' /
 ' /
!!
!!
?
?

$

 
5235,(7$5<,1)250$7,21
(  
(  

   
  

  + 
+ 
   3
   
+4
+4
 ! 
 ! 
 /
 
    
   
   
   
 
   
  
 
35,
235
52
352
35
(

      
                 
    !  
     !
   "
#  $ % " & '  (
     
        
          
           !     
 "         
 # $
    %
   
  &%

%
' ()(*+(,-
   
           
              
    !  " #$ " 
          
        #
&(/*(1(35
35
35235,(7
 
 
 
 
  ! 
 !
 
 

  
 
(7$5<,1)250$7,21
-
  
  
(7
(7
35

      
                 
    !  
     !
    "
#  $ % " & '  (
.
/(0*(12*(1345203(63/(3427(,6811(9./:6:6183(2:13427 8130)3
1;8,*03:810+9(.
   %
) '  
  + 
,   - 
 . /  % 01
  
4-  
6   
 '    
,! '   
, 
  + 
,   - 
 . /  % 01
   
4-  
 
6   
 '    
+  & 
      6: 
 
 8,8)09,4<
0;(37;;:9:03(
 ;;:)()8130)3
:1;8,*03:8159(06(
,(;(,383/((,:846
2=(,6(=(13
(58,3 8,*
 8*59(3:81
4:2(9:1(6
  ; 
  +  < 
,   - 
 . / 
8
01
; 
4- 
     %
(02 ) '  

  + 
,   - 
 . /  % 01
   
4-  
6   
 '    
&(/*(1(35235,(7$5<
  
  
 +
 +
,  
,  
 .
 .
8
$5
1(
5,(
1(
1(
1(
(1(
1
 
 %
*(
 '
 '
/*





*
< ,1)250$7,21
$7
1


50
50
,1)
< ,1
5<
<

      
                 
    !  
     !
   "
#  $ % " & '  (
,! '   
, 
  + 
,   - 
 . /  % 01
/81( %
 0A %

6   
 '    
+  & 
      6: 
 
 8,8)09,4<
0;(37;;:9:03(
 ;;:)()8130)3
:1;8,*03:8159(06(
,(;(,383/((,:846
2=(,6(=(13
(58,3 8,*
 8*59(3:81
4:2(9:1(6
  ; 
  +  < 
,   - 
 . / 
8
01
; 
4- 
&   %
   '  -  ' #        #  0 ! $
&(/*(1(35235,(7$5<,
$5
  #
  #  
,1)250$7,21
$7
$7
$7
$7
1)
,1)
< ,1

      
                 
    !  
     !
"   "
#  $ % " & '  (
.
/(0*(12*(1345203(63/(10*(8;)(13,0990+8,038,7:(6 01283/(,*(2:)09
012C8,3()/1:)092(50,3*(136 012C8,:163:343:816.
   %

    %

/*(1(35235,(7$5<,1)250$7,21
7$
235
35
1(
(1(
*(
/*
(/*
&(/
&(
&(
&

      
                 
    !  
     !
   "
#  $ % " & '  (
&   %     ! $
.
/(0*(12*(1345203(63/(8+G()3:=(6183(2:13/(71856:6012:16()3:81@8;
3/(5,838)89.
   %
 +G()3:=(6%
,:*0,7%

;        !          !       
# A    ! 0     !      0  # !  
           !    !    !  $
()8120,7%

;  #           !       # A    
! 0 !      $

;         !  9 !   ##   # ##   
! 0 !       0  # #   0      
    # A  $

;  #   B     C    !  0      
# A      $
 
 
 
    %
 +G()3:=(6%
,:*0,7%

;        !          !       # A 
   ! 0     !      0  # !         
    !    !    !  $

8 )8*50,( 3/( 5,8<,(66:81 ;,(( 64,=:=09    8; 9(109:28*:2( *8183/(,057 =(,646
:1=(63:<038,!6)/8:)(6:1<9(0<(13:1503:(136H:3/*0139()(9997*5/8*0  H/8/0=(
,(9056(20;3(,8,0,(,(;,0)38,738039(06301245385,:8,)/(*83/(,057,(<:*(16.
()8120,7%

8 2(3(,*:1( 3/( 8=(,099 ,(65816( ,03(    8; 9(109:28*:2( *8183/(,057 8,
:1=(63:<038,!6)/8:)(6:1<9(0<(13:1503:(136H:3/,(9056(28,,(;,0)38,7 .

 
 
  
 
1
 !
 ! 0
(1
   !
   !
*(
8

)8*
8*50
50
*
:1=(63:<
:1=(63:<
,(905
,(90
()8
()
5,(7$5<,1)250$7,21

  
 
#
# !
!
   #
   #
 ##

# 
#


  C  
 C    
$$
35,
235
23
52

      
                 
    !  
     !
5   "
#  $ % " & '  (

;  #           !       # A  
# A  6:1<9(0<(13  ! 0 !      $

;         !  9 !   ##   # ##   ! 
0 !       0  # #   0        
  # A   6:1<9(0<(13$

;  #   B     C    !  0      
# A      $
 
 
 


$   
&   %
; !   'D#  '     E   F,,G   E  !  4G9  4  
    '      #  !        0     
     $
E&   F,,G    #    !       'D#$
 
 
'.
/(0*(12*(1345203(63/(34271258:136183(2:13/(71856:6012:1
6()3:816 ?.012?.8;3/(5,838)89.
   %
34271258:136%
,:*0,7

F# !      ! !  I ,J9   ! !     I ,J9  
! !  I,J  '         +   !   > = ! 
  +>, J    9 ((( I    ((( +>, J$
()8120,7

&    ! 

   ##

;        ,    ,9  ,9 ,9  '  I&J 

;    !  

;      
&(/*(1(35235,
3/(
3/( 3427
34
3/(5,838)
/(5,838)
!  
!  

! 
!  I,
 +>, J  
 +>, J 
,7

&
&

7$5<,1)2
E  !
E  !
  

  'D#$
  'D#
0$7,21
0$
50$
250
25
)25
,(7
5,(7$

      
                 
    !  
     !
.   "
#  $ % " & '  (

;       ! 

F# ##  F



C     6F,;  CC 
    %
34271258:136%
,:*0,7

F# !      ! !  I ,J9   ! !     I ,J9  
! !  I,J  '         +   !   > = ! 
  +>, J    9 ((( I    ((( +>, J$

,8<,(66:81;,((64,=:=092(;:1(2063/(3:*(;,8*,0128*:I03:81383/(;:,638+6(,=03:818;
2:6(06(5,8<,(66:818,2(03/24(38017)046(.;3/(503:(13/061835,8<,(66(28,2:(2 
H:99+()(168,(2033/(3:*(8;9063)8*59(3(2066(66*(13H/(13/(503:(13H06E18H118338
/0=( 5,8<,(66(2. 03:(136 H/8 H:99 ,()(:=( 0 1(H 3,(03*(13 H:3/843 28)4*(13(2
5,8<,(66:81 H:99 +( )(168,(2 03 3/( 9063 066(66*(13 203( 3/03 3/( 503:(13 :6 E18H1 38 +(
5,8<,(66:81;,((.
()8120,7

 =(,099,(65816(,03()8*59(3(,(65816(J K)8*59(3(,(65816(41)81;:,*(2J 4K
01250,3:09,(65816(JK 066(66(2+70*82:;:)03:818;3/(13(,103:81097*5/8*0
"8,E6/85 ,:3(,:0" K /(681--- J/(,(0;3(,*82:;:(2---" K.

&    ! 

   ##

;        ,    ,9  ,9 ,9  '  I&J  

;    !  

;      

;       ! 

F# ##  F



C     6F,;  CC 
&   %
; !  !   '     F,,   49        '      
#  !        0          $
&(/*(1(35235,(7$5<,1)250$7,21
 
 I ,
I ,
50
J

,J
J
,
50
 !   
 !   > 
>
25
83/(
83/(;:,63
;:
1835,8<,(
1835,8<,(
(13/(503:(
13/(503
3,(03*(13
(03*(13
03(
03( 3/03
/03 3/
65816(
65816( J 
J 
6(2
6(2 +7
+7 0 *
 /(681--
 /(681
35
#
#
5
  ,  
  ,  
 
 
  
  
       
     
F# 
F# 




C

      
                 
    !  
     !
3   "
#  $ % " & '  (
.
/(0*(12*(1345203(63/(0)E<,841201203:8109(./:6:6183(2:13/(
71856:60)E<,841201203:8109( .
   %
K ;         '        # !    0 ! 
 0    #    '   !09    '   $$ 
# ! 9  ;F, '   $$    9 #  9 !    '   ' 1  '9 
LM     '   @  =9  N ) 9  N FA   9  K
K +               !  ! 0 !     
# 8?    8?9      !     O19  3$ +  (   
! 0  0 #'   !   9      !      'D# !  
   "P 0   ,   , $ ;             " # # 0  ! 
 P    '  !   P9    P9   P  '  !  P 
 O19  3$
/    !   '# 9     '     #  #  
         ! !    ! 0 !         !  $
    %
K ;         '        # !    0 ! 
 0    #    '   !09    '   $$ 
# ! 9  ;F, '   $$    9 #  9 !    '   ' 1  '9 
LM     '   @  =9  N ) 9  N FA   9  9  (66
-K
K +               !  ! 0 !     
# 8?    8?9      ?8;? !     >19  ($ +  
?   ! 0  0 #'   !   9      !      'D# 
!     "P 0   ,   , $ ;             " # # 0 
 !  P    '  !   P9    P9   P  '  ! 
 P  O19  3$ 'L C? . (2:01 5,8<,(66:81;,(( 64,=:=09    H06 .? *813/6.
 =(,0993/(5,:*0,76:2((;;()38; 9(109:28*:2(H06,(=(,6:+9( *7(986455,(66:81.,02(68,'
1(43,85(1:08))4,,(2:1'L3/,8*+8)7385(1:0:1-L01(*:0:1 -L0129(4)85(1:0:1?L8;
503:(136. /    !   '# 9     '     #  
#           ! !    ! 0 !       
  !  $
&   %  !
@.
/(0*(12*(1345203(63/(3427(6:<1. /:6:6183(2:13/(71856:6012:1
6()3:81B...
   %
;     19  !'9     !#    ! ++         
        0        !  0  # A   
   ! 0     !   0  # !            
 !    !     !$ ;             !    
&(/*(1(35235,(7$5<,1)250$7,21
 
 
(
(  
 
# ! 
# ! 
   !
 !
 !
 !

  # 
  # 
   
   
 
 
 #

09
09 

 9
 9 ! 
!
=9
=9  
N )
   !
   !


5
?
? 8;
8; 

!  
!  
 , 
, $ ;
23
!

  P
 P
2
C? .
C? . (2
(2
()3
()38;
8; 9
; (10
L
L 3/,8*
3/,8*
!
! 
 
  
  
  %
 %
*(


/(
/(
6(
6(
  
  
&
 

      
                 
    !  
     !
(   "
#  $ % " & '  (
   !       # A  $ ;     $ ; 
# A            !     !   0        0 
  '9 '9 - '9 '9    '$ ; #        
               ! !      1       $    
# A     0 #   !    0           ! # $
    %
;   *493:)(13(,9   19  !'9     !#    ! ++       
          0 8=(,        !  0  
# A      ! 0     !   0  # !     
        !    !     !  4 $ ; /(   0:*6   
      !  38)8*50,(3/(        !   8=(, 0     
# A  $ 
;     $ ; # A            !     ! 
  0        0   '9 '9 - '9 '9    '$ ; 
#                       ! !    
  1       $    # A     0 #   !    0   
        ! # $
&   %  !      0 !  !   4$       
  !  Q  Q"$
?.
/(0*(12*(1345203(63/(),((1:1<5/06(. /:6:6183(2:13/(71856:6 012
:16()3:81B....
   %
K H'   0 '    !  !! #       
    $    ! '       /        0 ' B 0 .    
      $  6'      '          /      
0         #    H  !   ' !     H' 
!    K
K$ +         '       ! ' =      ' =K
K6#        N" BB  ' 4+?   ' '         
  !     !  !$ ;     N" BB  ' 4+?   !   
       !      $ + #'9           9    
!   #09           &9  &9  & 9  & 9  & 9 /  K
    %
K H'   0 '    !  !! # 0))(53(2    
       $    ! '       /        0 ' B 0 . 
         $ (,898<7;8, 039(063 6<013: 6012013: ) 012;8,
  H:99+(,(M4:,(2066),((1:1<066(66*(13H:3/:1B20768;,0128*:I03:81:1(12(*:)0,(06$
6'      '          /  9  0126(,898<7  0  
       #    H  !   ' !     H' !   
 K
&(/*(1(35235,(7$5<,1)250$7,21


 
0:*6
0:*6   
$7
  
   

    
   
   '
   
 
 !

#
# 
  
 ! 

   4
   4
<5/06(.
<5/06(. /


  
  
/   
/   
   
  
#
#   
  
   ' 
   '
    
   
   !
   !

  
  !
!
#09  
#09  
 
 
/*
H'
H'
    
    
 
   
  
 
 

      
                 
    !  
     !
   "
#  $ % " & '  (
K +         '       ! ' =      ' = H/:)/H:99+(
,(34,1(2383/(8,:<:109:163:343:81N
K /(3,01698)03:813O' M%M +7  :6853:8109012:618364;;:):(1306689(5,88;;8,
2:0<186:6. 6#        N" BB  ' 4+?   )01 ' '    
       !     !  !$ ;     N" BB  ' 
4+?   !          !      $ + #'9           
9    !   #09           &9  &9  & 9  & 9 
 & 9 /  9 D:@?$
&   %
; 0   '   #    E!! #G   E!G     !! !$
      ?+L9 ?/L  ? L    ' =    !  '9  !   
         =      -   '  !#       
    ?+L9 ?/L  ? L$    ! Q"$
+     #    !  0 '       !  $
;    4+?   ' 0     !1     !  ! $
@5.      '   !        $
B.
/(0*(12*(1345203(63/(,(03*(135/06(./:6:6183(2:13/(71856:6 012
:16()3:81B...8;3/(5,838)89.
   %
F  '      '     !9 ! 0 '   1   
  #       !    # A  $ ;   ! 0  0 & 
             9     &      !$ ;    
      ! '    1 9 '  -     '0   1    &  "
9    !    B        ! !#  !   
  *!!  $.   $3$  0       !   !  9 
!'  -   #  00$ ; - 0 '    8 +  ; *6  
#               #      0 '  
   ;' .  ;' 3      K
          ;  H,+ # 5  R .      5    
  # (  R    0 ' !            
*               $       !!    
  !       !     !'  -   #  ! 
009  0 ! 9  ! 0     0! !$
&       ;  H,+ 0 ' #0          #0$
 
 
 
(/*(1(35235,(7$5<,1)250$7,21

9 
9 
 !
!
# 
#    
 
 $
$
 ! 
 ! 
 $
 $
/06(./:6
/06(./:
 
 
# A
# A
9     
9    
 9 
 9 ' 
'  
 


B 
 

 0
0
 
 00
0
  
  
;' 3
;' 3   
 

 

 
 R  

 

 

   
  

9  0 !
 0 !
  
  
&(/
&(
&

      
                 
    !  
     !
   "
#  $ % " & '  (
K  ,8668=(,;8,503:(136:13/(:1=(63:<038,6)/8:)(,*8197  
K ;  H,+        ' !   # (   R     !   
               $$  - I*   '     
 "(
;'JK
    %
F  '      '     !9 ! 0 '   1   
  #       !    # A  $ ;   ! ;8,(0)/503:(13
0  8163427 &              9      &      
!. ;           02*:1:63(,(2383/(503:(13:6)099(2  &$ ;  
        ! '    1 9 '  -     '0   1    & 
 " 9    !    B        ! !#  
!     *!!  $.   $3$  0       !   
!  9 !'  -   #  00$ ; - 0 '    8 + 
 ; *6  #               #      0 ' 
    ;' .  ;' 3      K
          ;  H:3/)813,063 H,+ H:3/)813,063 # 5  R . 
     5      # (  R    0 ' !       
     *               $       
!!      !       !     !'  -   
#  ! 009  0 ! 9  ! 0     0! !$
&       ;  H:3/)813,063 H,+ H:3/)813,063 0 ' #0      
    #0$
 6)016:63/(5,(;(,,(25,8)(24,(.; :6)813,0:12:)03(2:60))(530+9(.3:602=:6(238
63:)E383/(60*(5,8)(24,(;8,0<:=(1503:(133/,84</8433/(63427.
 
 
 
 
K  ,8668=(,;8,503:(136:13/(:1=(63:<038,6)/8:)(,*8197  
K  ;  H:3/)813,063 H,+ H:3/)813,063        ' !   # (   R  
   !                  $$  - I* 
'     "(
;'JK
&   %
;      &  ' 0     ' $
4    !!        '     ;  ,+ 0   !   $
;  ;      !        '  $ ,+  !'   ;   
 $
&(/*(1(35
136:13/(:1
36:13/(
,063
,063 H,+ 
H,+
!   
!  
   
  
(1
  
  
/*
   
   
4   
4   
  
5,(7$5<,1)250$7,21
 
 
503:(13
03:(13
$7
 
  

0$
$ ; 
$ ; 
    
    

 !#
!#
!
! 

 
 

 
  

H:3/
3/ )813,
)813
 0
0
'
'
  
  
! 
!  

   
  
H:3/)813,0
H:3/)813,0
813,0:12:)0
813,0:12:
33/,84</84
33/,84</84
35,
235
23
523
352

      
                 
    !  
     !
    "
#  $ % " & '  (
 
 
-.
/(0*(12*(1345203(63/( 8998H45/06(./:6:6183(2:13/(71856:6012
6()3:81B...8;3/(5,838)89
   %

 0      24(38,(0681683/(,3/015,8<,(66:=(8,,(9056(

  #     # 5        ! -   
 !     !

 ; H,+     # 5   R .    !     
! !   5              # (  R   
$
    %

 0      24(38,(0681683/(,3/015,8<,(66:=(8,,(9056(

  #     # 5        ! -   
 !     !

 ;  H:3/)813,063H,+ H:3/)813,063     # 5   R . 
  !     ! !   5              
# (  R   $
&   %
4    !!        '     ;  ,+ 0   !   $
.
/(0*(12*(1345203(63/(03081:38,:1< 8**:33((./:6:6183(2:13/(
71856:6012:16()3:81B.8;3/(5,838)89.
   %
* ! - &          &  0 #0         
         !   ! $ !      &  $ 
;    0      " ! # #           
#   !      !  $  ;      0    
   0    3 !   !     00 '    !  $ *  
  0      !   !     00 '    !  $
    %
* ! - &          &  0 #0         
         !   ! $ !      &  $ 
;    0      " ! # #            
#   !      !   $  ;      0     
&(/*(1(35235,(7$5<,1)250$7,21
- 
  


 ! 
! 
  (
(
 
 
15,8<
5,
,(66:=
,(66:=
  
 
3,063
3,063  
 
!
!  
 5   
$$
 ' 
 ' 
203(6
203(6 3/(
3/( 
(
()3:81B.8
()3:81B.
 &  
 &  
   
   
 0 
 0
 !   
 !  
0   
   
 0
 0
  
  
&(
*
* !
!



      
                 
    !  
     !
   "
#  $ % " & '  (
   0    3 !   !      00 '    !   $ *  
  0      !   !      00 '    !   $
&   %
4   &  #09   '      ' #     '    '      
             !        "     5 
  $ ;    !   !    ;   ,+   $
.
/(0*(12*(1345203(63/( 12(5(12(13A3(,10903/898<:)09(=:(H./:6:6
183(2:13/(71856:6 012:16()3:81B.8;3/(5,838)89.
   %
+         '       ! ' =      ' =$ +     
' =   ' 9 "       ' ' $ +  #     
#'   '  9   ' !  B$
6#        N" BB  ' 4+?   ' '         
  !     !  !$ ;     N" BB  ' 4+?   !   
       !      $ + #'9           9    
!   #09           &9  &9  & 9  & 9  & 9 /  K
    %
+         '       ! ' =      ' = H/:)/H:99+(
,(34,1(2383/(8,:<:109:163:343:81$ +     ' =   ' 9 "     
  ' ' $ +  #     #'   '  9   ' !  B$
/( 3,01698)03:81 3O' M%M  +7    :6 853:8109 012 :6 183 64;;:):(13 06 689( 5,88; ;8,
2:0<186:6. 6#        N" BB  ' 4+?   )01 ' '    
       !     !  !$ ;     N" BB  ' 
4+?   !          !      $ + #'9           
9    !   #09           &9  &9  & 9  & 9 
 & 9 /  9 D:@?N
&   %
+      !   !        !   '   0 '  
'=    # A    #0$
;  !  4+?  # ' 0     $
@5.  '   !        $
.
/(0*(12*(1345203(63/( 4*+(,8;03:(136. /:6:6183(2:13/(71856:6.
   %
8 '   !  !    *  *9   *  /
    %
8 '   !  !    *  *9   *  / 055,8A:*03(97@?,0128*:I(2503:(136
&(/*(1(35235,(7$5<,1)250$7,21
:6:6
6:6
 =$ 
 =$ ++ 

#
# 

   
 

B  ' 4
B  ' 
   
   
 & 9  &
 & 9 
 
 ' = 
' =  
= =   
  '
'   ' 
'   '
 :6
:6 853:81
853:81
N" BB
N" BB
 
  !

 
 
   
  !  
! 
23
9 
  
 
 !  
 ! 
 A  
 A  
?  
?  
  
  
/
/
  
  
&
 '

      
                 
    !  
     !
"   "
#  $ % " & '  (
&      ! # 0      -!  ! 1$
.
/(0*(12*(1345203(63/( 3427854903:811)946:81 ,:3(,:0./:6:6183(2
:13/(71856:6 012:16()3:81-.8;3/(5,838)89.
   %
K  0  # ! 9 !            9  !    !  
  !  9  0  #    ! #   ,    !  
  !        #    ,   ,   !   K
K  #  '          '  ;H,+           
      '  0  !!   K
    %
K   0  # ! 9 !            9  !    !  
  !  9 H/80,(,(;,0)38,7383/(:,,(<:*(18,/0=(,(9056(281)(8,45383/,((
3:*(6  0  #    ! #   ,    !    !    
    #    ,   ,   !   K
K  #  '          '  ;H,+ 8,:; :6
)813,0:12:)03(2                  '  0  !! 
  K
&   %
6'   '  !        '            !  
  !  $    !  '    !    $
; !        ; $ ;      ' !  $    
    !  Q3$
'.
/(0*(12*(1345203(63/( 3427854903:81A)946:81 ,:3(,:0./:6:6183(2
:13/(71856:6 012:16()3:81-.8;3/(5,838)89.
   %

@ 0  ! #     # #   0       #  ?+L9 
! / #  ?/L   !   #  ? L$   0    ! # '   
! / # #  '

 0     0   = &L; ! !-

     ' #     -!   !  S   H   
B#   !!        

*        0 '   '  

*'   !    *8  T9 H    $ - (H

   T 59H   5 - (H
&(/*(1(35235,(7$5<,1)250$7,21


9  !   
9  !  
)2
281)(8,4
281)(
  ! 
  !
,+
,+
<
8,
8
 ' 
 '
  ' 
'


  ! 
  ! 
   
  
5203(6
203(6 3/(
3/(
012:16()3
012:16(
 ! # 
 ! # 
 / #  
 / #  
! / #
 / #
 0
 0



B
B


      
                 
    !  
     !
   "
#  $ % " & '  (

  !    *;H)F;       *;H); U $ - 
!!         :8$

    '' V  $  H  " W  H9 -!         

       = )      T   H 
    %

@ 0  ! #     # #   0       #  ?+L

@ 0  ! #     # #   0 ! / #

 6<586:3:=(.

 6<1(<03:=(013: 6586:3:=(012C8,013: )586:3:=(0122(3()30+9(=:,09
 .

03:(136H/80,( 6<1(<03:=(012=:,09 1(<03:=(0,((9:<:+9(.

03:(136H/8/02/(503:3:6+43/0=(,()(:=(201013:=:,093,(03*(130126/8H18
2(3()30+9(=:,09 ;8,@*813/60,((9:<:+9(.

03:(136H/80,(6(,8586:3:=(+()046(8;/(503:3:6=:,46=0)):1(0,((9:<:+9(.

@ 0  ! #     # #   0 !   #

03:(136H/8/02/(503:3:6 +43/0=(,()(:=(201013:=:,093,(03*(130126/8H18
2(3()30+9(=:,09 ;8,@*813/60,((9:<:+9(.

03:(136H/80,(183 0   = &L; ! !-9 :;3/(70,(03,:6E6((2(;:1:3:81:1
6()3:81..@ 

     ' #     ?20765,:8,38,0128*:I03:819 -!   
!  S   H   B#   !!        

*        0 '   '  

*'   !    *8  T9 H    $ - (H

   T 59H   5 - (H

  !    *;H)F;       *;H); U $ - 
!!         :8$

(,4*0650,303(3,0160*:106(C  8,0901:1(3,0160*:106(C 
P.A455(,9:*:38;18,*09  (A)(53:1503:(136H:3/28)4*(13(29:=(,
:1=89=(*(13+797*5/8*0

    '' V  $  H  " W  H9 -!         

(,4*38309+:9:,4+:1P.A (A)(53:1)06(8;:9+(,3!6712,8*(012
28)4*(13(29:=(,:1=89=(*(13+797*5/8*0.

       = )      T   H 
&(/*(1(35235,(7$5<,1)250$7,21
  ?+L
 ?+L
122(3()30+
122(3()30+
3:=(0,((9:<
=(0,((9:<
013:=:,093,
013:=:,093,
(503:3:6=:
503:3:6
  0 !
  0 
/0=(,()(:=(
/0=(,()(:
13/60,((9:<
13/60,((9:<
= &L; !
= &L; !
#  
#  
   B#
   B#
    0
   0
  !
  !
   T
   T
  !
  !
(1
!! 
!! 
*(

(
(

      
                 
    !  
     !
5   "
#  $ % " & '  (
&   %
6-   #   !#           ?+L9 ?/L  ? L  ' ' 
    !! $
&L; ! !-           !9      =9      $$5   
 !   9 A 0     ' !$
6-            .  0  !    !    !$ 
; !!     '   # #  ' !    0 ;' 5        
    $ +   !          #   *;H*; 
     ! 0     '   !!$
.
/(0*(12*(1345203(63/( 3427,4<4559:(6./:6:6183(2:13/(71856:6
012:16()3:81.8;3/(5,838)89.
   %
4 /                0  #K
    %
4 /                0  #$  (093/)0,(
5,8=:2(,66/8492)816:2(,H(0,:1<<98=(6H/(12:,()397/0129:1<(=9:*:29(109:28*:2( )05649(6
;8998H(2+7630120,2/012H06/:1<N
&     %            !     
!$
@.
/(0*(12*(1345203(63/(66(66*(136;;:)0)7./:6:6183(2:13/(71856:6
66(66*(136;;:)0)7 .
   %

F# !    ,   '   '         +  
> = !  !   ,!       9 ((( I    +>,  J

&          !  

 ; 0  H,+  !    '  # 5   R.   & 9 
       5      # (  R       K
    %

03(8;28)4*(1303:818;2:6(06(5,8<,(66:81

F# !    ,   '   '         +  
> = !  !   ,!       9 ((( I    +>,  J

4*8,)813,89,03(  48, 
&(/*(1(35235,(7$5<,1)250$7,21
    
    
H*;
H*;
(2:13/(
(2:13/(
  #
  #
  0
  0
$5
/0129:1<
/0129:1<

 

6 3/(
3/( 66(
6
(
7 .
7 .
   ,  
   
 !   ,
 !   ,
   
  
; 0  
0  
    
    
 

(/*




      
                 
    !  
     !
.   "
#  $ % " & '  (

 ; 0  H,+ H:3/)813,063  !    '  # 5   R.  
 & 9        5      # (  R     
  K
&   %
&          !    '   #   ' !         
!   'D#  !   4$
;       #        !   $
4    !!        '     ;  ,+ 0   !   $
?.
/(0*(12*(1345203(63/( 303:63:)0910976:6%0*59(:I(./:6:6183(2:1
3/(71856:6 012:16()3:81.B8;3/(5,838)89.
   %
;    'D#           F# ,!  ,  F,,$
 ! 1    '    0    (P   #     !  
    F,,       #K
K :     !    0  $ 0   #   ! 1    ! 0 
# 3P ! 0      '0  8 !  ! !      P   
# ! !      P
*         !#        ! 1   0 '         
 $ >       !         $
    %
;    'D#           F# ,!  ,  F,,$ 382(*8163,03(3/(
(;;:)0)78;9(109:28*:2(8=(,01:1=(63:<038,!6)/8:)(6:1<9(0<(13+06(281 .
/(5,:*0,7010976:6:638)8*50,( +(3H((19(109:28*:2(012:1=(63:<038,!6)/8:)(
*8183/(,057. 8,3/(5,:*0,7(;;:)0)7=0,:0+9( 0/0I0,2,03:8  8;.?9(02:1<3801
:*5,8=(*(13:1*(2:01 ;,8*.*813/6;8,3/()813,890,*38039(063'.*813/6;8,
9(109:28*:2(:6)816:2(,(2)9:1:)0997,(9(=013.
/(6(0664*53:8160,(64558,3(2+7,()(13203054+9:6/(2:1,(9056(2,(;,0)38,7 .
":3/0/0I0,2,03:88;.?;499:1;8,*03:811()(660,7;8,081(6:2(298<,01E3(63H:3/018=(,099
095/08;.38/0=(BL58H(,H:99+(0)/:(=(2H/(1055,8A:*03(97B503:(136/0=(
5,8<,(66(28,2:(2.
/(60*59(6:I(:1:3:0997H06)09)4903(238(63:*03(3/( =(,099(65816(03(  /8H(=(,:3
,(*0:1602(M403(38(63:*03( .
 ! 1    '    0    (P   #     !  
    F,,       #K
K:     !    0  $ 0   #   ! 1    ! 0 
# 3P ! 0      '0  8 !  ! !      P   
# ! !      P$
 8;8,*0960*59(6:I()09)4903:81H:99+(281(;8,3/()813,890,*.":3/0%,03:8503:(1360,(
1((2(2:13/()813,890,*.
&(/*(1(35235,(7$5<,1)250$7,21
!   $
!   $
/:6:6183(
/:6:618
F,,$
,,$
#  
#  
 #  
#  
!  ! 
!  !
 !
 ! 1
1
    
    
   F#
   F#
23
(63:<038,!6)
3:<038,!6
0,( +(3
0,( +(3
7(;;:)0)7=
7(;;:)0)7=
;,8*.
;,8*.
(2)9:1:)0997
(2)9:1:)09
,(64558,3(
(64558,3
:88;.?;4
:88;.?;4
8/0=(BL
8/0=(B
,2:(2.
,2:(2.
59(6:I(:1:3:
6:I(:1:
1602(M403(
1602(M403(
 ! 1 
! 1 
 
    
    
:
:


      
                 
    !  
     !
3   "
#  $ % " & '  (
664*:1<3/03L8;503:(136H:99+(986338;8998H45@?503:(136H:99+(,0128*:I(2.
*         !#        ! 1   0 '         
 $ >       !         $
&   %
   !     !   'D#H!  $
  '  -!   1 !  !         0!9     
#        !   $
B.
/(0*(12*(1345203(63/( ;;:)0)7010976:6./:6:6183(2:13/(71856:68;
3/(5,838)89.
   %
;      # !     ,9  ,  ,$ ; +  > = ! 
 !   ,!     +>,     9 (((9     ' 4    5N @    . 
     0 '       $  ;' .     !     
   $ ;   0 ' #0 '  ! #0    $ ; !  
 0 '        +;; ! !     # !  9 !  
##9   # ##$ * ! 0  # #            & 
0              ? =A  !   0 '    
# $
4     

&    !  0 '            !     ,  
      !     $  0      !         
0 '  $ ;  0 '    !  !$

   ##           1    'D#    
!          $  0      !         0 
'  K$
K 6  0 '   0  ! #   !   5          
  '    ! 5   $ 
* !        # !    # ## 0 '           0 !$ 8  
D     !           !# $
*   0 '         'K
    %
;      # !     ,9  ,  ,$ 5,8<,(66:81;,((64,=:=09  . 
:62(;:1(2063/(3:*(;,8*,0128*:I03:81413:98+G()3:=(34*8,5,8<,(66:818,2(03/;8,017
,(0681. 03:(136H/8281835,8<,(66033/(3:*(8;010976:6H:99+()(168,(2.,8<,(66:81H:99+(
2(3(,*:1(20))8,2:1<38  +  > = !  !   ,!     +>,     9
(((9     ' 4    5N @    .      0 '       $ 
 ;' .     !        $ ;   0 ' #0 '  
&(/*(1(35235,(7$5<,1)250$7,21
56:6
56:6 8;
8;
> = ! 
> = !
   5N @
  5
!    
!   
0    
0    
!  
!  
   
   
  !  
 !  
     
    

$ 
$ 
 ' 
 ' 
  
 
  $
  $
'  
'  
  ! 5 
 ! 5
    #
    #
 !
 !
  0

 
 
(/
;
 

:62(;:1(
62(;:1
68

      
                 
    !  
     !
(   "
#  $ % " & '  (
! #0    $ ; !   0 '        +;; ! !  
   9  # !  9 !  ##9   # ## 0126()8120,7(1258:136$ 
* ! 0  # #            & 0     
         ? =A  !   0 '    # $
4     

 =(,099,(65816(,03(  4012 

&    !  0 '            !     ,  
      !     $  0      !         
0 '  $ ;  0 '    !  !$

   ##           1    'D#    
!          $  0      !         0
'  $
K 6  0 '   0  ! #   !   5          
  '    ! 5   $ B2(03/68,5,8<,(66:816/0=(8))4,,(2.
* !        # !    # ## 0 '           0 !$ 8  
D     !           !# $ H:99+(0559:(2$
*   0 '         '$
/(D05901(:(,5,8)(24,(H:99+(46(238)/0,0)3(,:I(3:*(38(=(13(1258:13601224,03:818;
,(65816(.(2:013:*(638(=(130123/(:,,(65()3:=(3H86:2(2-L)81;:2(1)(:13(,=096H:99+(
5,8=:2(2;8,(0)/8;3/(6(=0,:0+9(6.14163,03:;:(298<,01E3(63H:99+(46(238)8*50,(
3,(03*(130,*6;8,3:*(38(=(13=0,:0+9(6./( 8A5,858,3:8109/0I0,26,(<,(66:81*82(9H:99+(
46(238066(663/(6:<1:;:)01)(8;63,03:;:)03:81;0)38,6813,(03*(132:;;(,(1)(6.
; @! !  0 '    1     # !       
! $    #   !# 0  (P   # 0 ' ! # 
      #'$ 
&   %    !     !   'D#H!  $
-.
/(0*(12*(1345203(63/(13(,:*010976:6012 ./:6:6183(2:13/(
71856:6012:16()3:81.?8;3/(5,838)89.
   %
* ! - &          &  0 #0         
         !   ! $ !      &  $ 
          0 ' !!   &          &  #0$ ; 
   0      " ! # #           
#   !      !  $  ;      0     
   0    3 !   !     00 '    !  $ *  
  0      !   !     00 '    !  $
4  0 '   0 !! -  3 !   !     0 0 '  
  !      " !   ,#  $
&(/*(1(35235,(7$5<,1)250$7,21
 
 
    
    
50
   
  
50


50
5      
     
)2
))4,,(2.
4,,(2
   
  
H:99+(0559
9+(055
3:*(38(=(
*(38(=
H8
H86:2(2-
6:2(2-
298<
98<,01E3
,01E3
 8A5,858,
 8A5,858
;0)38,681
;0)38,681
1
1
35
 !#
 !
23
  !
  !
*(1
*(13452
3452
012:16(
012:16(
 %
 %
(
 
 -
-
  


   

  
 

#  
#  
  
  


      
                 
    !  
     !
    "
#  $ % " & '  (
/    (P + !! 9   !! '   ' 0   P       9  &  
       !!  $ 
    %
* ! - &          &  0 #0         
         !   ! $ !      &  $ 
          0 ' !!   &          &  #0$ ; 
   0      " ! # #            
#   !      !   $  ;      0    
    0    3 !   !      00 '    !  
$ *    0      !   !      00 '  
  !   $
4  0 '   0 !! -  3 !   !      0 0 
'    !       " !   ,# 9(109:28*:2(  $
 H:99)8124)301010976:6;8,;43:9:3781 012 =(,099,(65816(,03(. 865():;:)63855:1<
,49(6H:99+(<:=(1383/( ;8,3/( 3/(;8998H:1<,49(6*:</3+(46(2;8,8=(,099,(65816(
,03(.
06(2810-L 055,80)/:;3/(455(,+8412:6+(98HL:13/(9(109:28*:2(0,*3/( 
6/8492,()8**(1263855:1<3/(3,:09.
&   %
   !     !   'D#H!  $
8 '     '          0         $
&(/*(1(35235,(7$5<,1)250$7,21
 


 
$7

0 
0 '
'  
 
  0 0
0 0
 865():;:)6
 865():;:)
(2;8,8=(,
2;8,8
(9(109:28*
9(109:28*
H!  
H! 
 0  
0  

      
                 
    !  
     !
    "
#  $ % " & '  (
.
/(0*(12*(1345203(63/( )/(249(8;342766(66*(136./:6:6183(2:13/(
71856:6)/(249(8;342766(66*(136 0+9(.
    '     "(
0+9(%
)/(249(8;342766(66*(136 ;8,,*012,*503:(136 B2076Q
)7)9( 
,8)(24,(
),((1:1<C06(9:1(
B076 
=(,7 7)9(07R
2076
 7)9(
07'B
 7)9(6'07 R
207
=(,7@2076;3(,
 7)9(07
R?2076;8,3/(;:,63@
*813/60123/(1(=(,7
-2076R2076
3/(,(0;3(,
3,(03*(13
:6)813:1403:81
 8998H45;8,503:(136
0;3(,
 8998H45;8,181
503:(136
+ H-  
S
   !    
S
 8  !   6# 
S
  +     +- 
 ++ 
S
   !   !
S
       = 
)   
S
  6 )"
S
 !        ' ! 
!  
S
6    !# F   ) !
 6 F) !   
S
S
S
L 5
S
S
S
 /  0 &.
S
S
S-
S-
S
    3
S
S
S-
S-
S
   ?/L9 ? L    

S
;    .
S
 ;  4/   
S
S
S
S
S
       
'    +    
 
S
S
S
S
*     !   
 !  
S
S
S
*# 6#
S
S
S
S
S
S'
S'
,  ? !1 
S
S
;   4 H ;    
* 
S
       H 
S
S
S
S

:6
:6
 8998H45
 8998H4
0;3(,
0;3(,

45;8,181
45;8,181

250$7
2
)2
1 2
1
< ,1
5<
$5
7$
7$
7$
7$
(7$
(7
(7
(7
5 (7
235
35
S
35
35
235
52
52
523
23
S
23
52
52
352
352
S
52
52
52
52
52
352
52
35
35
S
5
35
35
(3
( 3
(

1( 3
1(
1(
(1
 4/   
(1
*(
   

/*(
   +
(/*(
(/*
    
&(/
 !  

(/*
&(
*

&(
&

      
                 
    !  
     !
     "
#  $ % " & '  (
,8)(24,(
),((1:1<C06(9:1(
B076 
=(,7 7)9(07R
2076
 7)9(
07'B
 7)9(6'07 R
207
=(,7@2076;3(,
 7)9(07
R?2076;8,3/(;:,63@
*813/60123/(1(=(,7
-2076R2076
3/(,(0;3(,
3,(03*(13
:6)813:1403:81
 8998H45;8,503:(136
0;3(,
 8998H45;8,181
503:(136
 -  5
S
S
S
S
S
 ; 0   8, ,+ 0 
  :; )813,0:12:)03(2    
=9 9 '    !#3
S@
SB
SB
;      
  3
S
SB
,!   
SB
  4 ##(
SB
S
S
 ,!#         ?X6   )    !!            & 
   9  '    0     ' =    !        ! '9 !' '  
  1              !  9 '    3 0=    1 $ + ! 0     
 #     &9 #    #-!      &    &  !'$ * 9  !!   
   ' 4+?    !     !  !  ' '       9  #'$ +    
          !   #09           &9  &9  & 9  & 9  & 9 
/  9 D:@?$ +      ' =    ' 9 "  9       ' ' $ +  # 
    #'   '  9   ' !  B$ 
  197;8,503:(136:1,*012503:(136:1),8668=(,%+(;8,(    4     '   
 4 /          '      '   9    # 0  # !  !  
     ;  !    ' !   0 "  !         9   
  !    ' !   0  "   !         $ ; !     #  
   +#   #       !   #$ * ! 0 ' 0  
    ! '  0 '   '  ! !   !  =    -! $ 
  !  '  *!!  $.   $3$
  197 ;8, 503:(136 :1 ,*  012 503:(136 :1 ),866 8=(,% 24,:1<   !!      3    0 
        4 /      # 0  !    !  '  *!!
 $.   $3$ +      B ! 9  #       0 4 /      
   '      '      #   !  '  *!!  $.   $3$ 
  197;8,503:(136:1,* 012503:(136:1),8668=(,%099503:(136   '   '  ! !   
=    -! $ 
  197;8,503:(136:1,* 012503:(136:1),8668=(,%0;3(,B  !        $
3  ; 0  H,+ H:3/)813,063   ' !   # 5   R .  !   5             
 # ( R  9     0 ! !   ! 0  #       # 
# 0  #   ! # $  ;  H:3/)813,063 H,+ H:3/)813,063        ' !   
   0!   ! 0        !     !$ 
 
 
 
 
 
 5   +   ;    ,+ 0   0  3              ,0128*:I03:819    ;    ,+ 
    #   ' !      $
&   %
&(/*(1(35235,(7$5<,1)250$7,21
0$7
$
0$7
50
50
50$
0$
0$
50$
25
250
50
50
250
)2
)25
25
25
)2

 
 

 

    

   1
 
!'$ 
!'$ *
'  
'   
  
  
 
 

(7
(;8,(
(7


  '   
  '  
!   0
!   0
  !   
  !  
    !
    !
  
 ' 
' 
$.   $3
$.    $
523
36
),86
  
  

B !
 !
    
    
35
503:(
:
1(
 012503
1(
/)813,063

 

#   !
#  
0!   !
!   !
*(
/*(
(/*
&(/
&(
&

      
                 
    !  
     !
    "
#  $ % " & '  (
   ;'       0  !   $ 
* 0 0      '    #    -'    #  &     9    
 "$
     4/     !!'   ! #     *  *     #$
.
/(0*(12*(1345203(63/( )/(249(8;342766(66*(136;8,503:(136H:3/
),8668=(,./:6:6183(2:13/(71856:6)/(249(8;342766(66*(136 0+9(

    '     "(
0+9(%
)/(249(8;63427066(66*(136;8,503:(136H:3/),8668=(,819(109:28*:2(
0;3(,5,8<,(66:81:1:1=(63:<038,T6)/8:)(,*B2076Q)7)9( U 8
*8,(3/01H((E60;3(,90632078;9063)7)9(8;3,(03*(13:1,*
,8)(24,(
=(,7 7)9(
07R2076
 7)9(
07'B
 7)9(6'
07
=(,7-2076;3(,
 7)9(07
R2076
3,(03*(13
:6)813:1403:81
 8998H45;8,
503:(1360;3(,
 8998H45;8,181
503:(136
6    !# F   ) !  6 F) 
!   
S
S
L 
S
S
 /  0  
S
S
S
S
    
S
S
S
S
 ;   4 /"
S
S
/    H       
(109:28*:2( 8416(9:1<0122:63,:+43(
9(109:28*:2(1;8,*03:81/((3
S
&'      
S
S
:65(16(634272,4<
S
34272,4<,(34,1
S
S
*# 6#5
S
S
S
S
S5
;   4 H;    * .
S
,  ? !1 
S
S
       H  
S
S
S
S
 ; 0   8, ,+ 0  9 :; 
)813,0:12:)03(2    =9 9 '    
!#
S
S3
;        
S
,!   
S
  4 ##(
S
S
S
&(/*(1(35235,(7$5<,1)250$7,21
(
09:28*:2(
09:28*:2
)7)9( U
)7)9( U  8
 8
U
:1,*
:1,*
0

=(,7-
=(,7-
 7)9(07
 7)9(07
2076
20
*(13
(13
:81
81
)2
)2
)2
$5
,1)2
)2
$5
$5
$5
(7$5
(7
(7
(7
(7
S
5,(
5 (
S
5
35
S
35
35
35
35
3
S
23
523
 
 
35
( 3
1(
(1
    *
    *
*(
!
! 1 
1 
/*
   
   
(/*
&(
; 0  
&(
13,0:12
&
#
&(

      
                 
    !  
     !
 "   "
#  $ % " & '  (
,8)(24,(
=(,7 7)9(
07R2076
 7)9(
07'B
 7)9(6'
07
=(,7-2076;3(,
 7)9(07
R2076
3,(03*(13
:6)813:1403:81
 8998H45;8,
503:(1360;3(,
 8998H45;8,181
503:(136
F# ##
S
S
3 ; 0  H   ,+ H:3/ )813,063      (   R       0 ! !   
! 0  #        # # 0  #   ! # $  ; 
 H:3/ )813,063 H,+ H:3/ )813,063        ' !      0!   ! 0  
      !     !$ 
&   %
   ;'  # '     '      0 ;'  $
.
/(0*(12*(1345203(63/(9:638;++,(=:03:8160125():09:63(,*6./:6:6
183(2:13/(5,838)89++,(=:03:8160125():09:63(,*6 0+9('.
   %
 ;
   !1 *- ;   !
    %
 ;
   !1 *- ;   !
 
 0I0,203:8

0<1(3:)(68101)(*0<:1<
&   % ?,  ,+ 0   0  ?,      ,+   !#  !   $ 
; ''#     ; 0 #       0  !! !    $
.
/(0*(12*(1345203(6013(9 (997*5/8*0./:6:6183(2:13/(5,838)89:1
6()3:81..
   %
? 0#9  !       ! 0 !     !           
 #  ## !! $ ;         '        
# !    0 !  0    #    '   !09 
   '  I$$ # ! J9  ;F, '  I     >19  9 
#    ?9  .J     ' $ ; 0 ! !!  
# '   ! !#   0 #    @  =9  N ) 9  N 
FA   9  $ ;   '     0 !           
!      =                   ! 
 Y9  3$
    %
&(/*(1(35235,(7$5<,1)250$7,21
7,
7,
7,
   
 
$ 
$  ;
 ;

 0
0 
5():09:63
5():09:63
(,*6 0+
(,*6 
!
!
5<
$5
-

(
; 
;   
  
(7
:8:8
,(
3:)(68101
3:)(681
5
23
  
 
      
      
*(13452
*(1345203
.
%
(
    
    
##
# !!
!!
  
 
  
  

 
 

  
    
#

'
'
  
  
&

      
                 
    !  
     !
    "
#  $ % " & '  (
? 0#9  !       ! 0 !     !           
 #  ## !! $ ;         '        
# !    0 !  0    #    '   !09 
   '  I$$ # ! J9  ;F, '  I     >19     (66
-9 #    ?9  .J     ' $ ; 0 ! 
!!  # '   ! !#   0 #    @  =9  N
) 9  N FA   9  $ ;   '     0 !      
     !      =                 
  !  Y9  3$
&   %  !$
'.
/(0*(12*(1345203(6 9:1:)09342:(68;9(109:28*:2(:1 81 82<E:1!6
7*5/8*0./:6:6183(2:13/(5,838)89:16()3:81...
   %
K +      8? 0 0   8 # '  59     3 !    
 $  *    9  39 (   ! 0 #'   !     O19  3$  
;    0 55  %3  $ ;                    
0 $"  $"%( $  ; !  #        %3 !   9   P  (H( 
  !  # !  ' 1  '  $  ; F,,      0 "P  5H(9 
 P  H(   ! !    ,H    ,9   3P  H( ! ! $  ; 
  5P !  ' $  ;             " # # 0  !  P 
   '  !   P9    P9   P  '  !  P  O19 
 3$
    %
K +      8? 0 0   8 # '  59     3 !    
 $  *    9  39 (   ! 0 #'   !     O19  3$  
;    0 55  %3  $ ;                    
0 $"  $"%( $  ; !  #        %3 !   9   P  (H( 
  !  # !  ' 1  '  $  ; F,,      0 "P  5H(9 
 P  H(   ! !    ,H    ,9   3P  H( ! ! $  ; 
  5P !  ' $  ;             " # # 0  !  P 
   '  !   P9    P9   P  '  !  P  O19 
 3$ ? 503:(136 H(,( (1,899(2. 1 3/( ?   503:(136 H/8 H(,( (=0940+9( ;8, ,(65816(
066(66*(13   9(109:28*:2( 3/(,057 9(2 38 01 8+G()3:=( ,(65816( ,03( 8; 'L C? . (2:01
5,8<,(66:81;,((64,=:=09  H06.? *813/6.  =(,0993/(5,:*0,76:2((;;()38; 9(109:28*:2(
H06,(=(,6:+9(*7(986455,(66:81.,02(68,'1(43,85(1:08))4,,(2:1'L3/,8*+8)7385(1:0:1
-L01(*:0:1-L0129(4)85(1:0:1?L8;503:(136.":3I:<- 
&   %  !$
&(/*(1(35235,(7$5<,1)250$7,21
  
  
 82<E:1
 82<E:1!6
    3 !
    3 !
 
 


     
     
 
 %3 ! 
3 ! 
F,, 
,,   
 ,9   
 ,9   
    " 
    " 

  P 
 P 
0 
0 
 !
! 0
23
$ ;  
$ ;  
52

  

35
  ' 1 
' 1 
3
 !
 !
( 3

 

! 
!
( 3
' $ 
 
1(

   P9
  P9
1
:(136
:(136 H(,(
H(,
9(109:28
(109:28
81;,((
;,(( 64,
64
(=(,6:+9(*
=(,6:+9(*
L01(*:0:
L01(*:0
& 
& 
&

      
                 
    !  
     !
 5   "
#  $ % " & '  (
.
/(0*(12*(1345203(6(6:<103:8109(./:6:6183(2:13/(5,838)89:16()3:81
B.
B..(6:<103:8109(
   %
;      #          !  ! 0 
!        !  $ ;        ! #  
    =   #  !!'$  '     0   
      ! ! $   B   #  '      
     ! 9  !   ! $
    %
;      # (=09403(          ! =(,646
:1=(63:<038,!6 )/8:)(  ! 0 !        !  $ /( 5,:*0,7
(;;:)0)78+G()3:=(:6+06(281 .
;        ! #      =   #  
!!'$  '     0         ! ! $ 
  B   #  '           ! 9 
!  6()8120,7  ! $
&   %  !      0 !  !   4$       
  !  Q  Q"$
@.
/(0*(12*(1345203(6 ,8668=(,;8,503:(136:13/(:1=(63:<038,6)/8:)(,*
8197 ./:6:6183(2:13/(5,838)89:16()3:81B....
   %
;  0    0        #     -   !      *  / 
#  #    H-       $$ '   ! 9 '      
 0=           *  /$
    %
;  0    0        #     -   !      *  / 
#  #    H-       $$ '   ! 9 '      
 0=    9063207        *  /$ 
&     % !       -   0 '     #   *  * 
      '             *  /  # A  $
?.
/(0*(12*(1345203(6 8998H45/06(./:6:6183(2:13/(5,838)89:16()3:81
B...'.
   %
&(/*(1(35235,(7$5<,1)250$7,21
 
 
 


 
 !
!  $ 
!  
/(
/(

 
 =
=
  





  ! 
  ! 
=(,;8,50
=(,;8,50
838)89:16
838)89:16
 
    
  
  
  

  
   

  
   0
0
  
 
 
 
(
906320
9063
  
  %
*(
    
   

      
                 
    !  
     !
 .   "
#  $ % " & '  (
K$ ;   0 ! ! 0     .P    ! #         0! 
 !  !  V             !    # !    ,H ,  
' 9 0 #    9  0     0 '  $
8 '   ! !! -   !    *  *9   *  /$
    %
K$ ;   0 ! ! 0     .P    ! #         0! 
 !  !  V             !    # !    ,H ,  
' 9 0 #    9  0     0 '  $
8 '   ! !! -   !    *  *9   *  /$
&   %
;  '    '   !  '     !! !    $
B.
/(0*(12*(1345203(612(5(12(13(=:(H 8**:33((  ./:6:6183(2:1
3/(5,838)89:16()3:81B.'.
   %
; +,     !    0  -     0        D    # 
   9     H   $  ; +,  0 !    '9 !     
   !        &  &9 #0     !      
   !      !$ ;  #0 '  +,  0 '    !  
     0 '       ,! $ 4    ! 
     ,   $
    %
:0<1863:):*0<:1<,(64936 H:3/)813,063CH:3/)813,063 H:99+(,(=:(H(298)09970120968
6(1338 ;8,)(13,09,(=:(H. ; +,     !    0  -    0    
    D 9   #    9     H   $  ; +,  0 !    '9 
!        !        &  &9 #0     
!         !      !$ 
*   #0 '  +,  0 '    !       0 ' 
      ,! $ 
4    !      ,   $
&   %             #   '  9 !   
  ! #0$
-.
/(0*(12*(1345203(6 =(,=:(H8;2860<(8;1=(63:<038,!6)/8:)(2,4<6./:6
:6183(2:13/(5,838)89:16()3:81.. 412(,0+9(
   %
&(/*(1(35235,(7$5<,1)250$7,21
0!
!
, 
 
   
   
*:33((
3(( 
 
  
  
  
   '
 '
 
&9 #0
&9 #0
 #0
#0
 
  
 
3/
3/)813,06
)813,0
;  +, 
+, 
 #   
#  
  
  
   
   
0 
0 ' 
' 

  
  
 !
 !
 
 
(/*
 
 
-

      
                 
    !  
     !
 3   "
#  $ % " & '  (
Q ,- '       ' ! # 5   & 5  #         # 5 
 $ 4   !#     =       0      ,- ' 
U       !     B#  !    &
    %
Q ,- '       ' ! # 5   & 5  #         # 5 
 $ 4   !#     =       0      ,- ' 
V       !     B#  !    &$
03:(136:1,*1((238;8998H3/(6)/(249(2=:6:36062:65907(2:10+9(. 8,68*(2,4<6
022:3:8109=:6:36*07+(1((2(2.
&   
       !       #    -    1      !  $
4  *  /9       #9   - !   ,- '   # 5  
  #  '    '0     0  $
.
/(0*(12*(1345203(6 860<(82:;:)03:81;8,(109:28*:2(./:6:6183(2:1
3/(5,838)89:16()3:81..0+9(@.
    '     "(
0+9(@%
860<(82:;:)03:81;8,(109:28*:2(
    
8A:):37,02(
)3:81(M4:,(2
*     !#
)  
) "

?   !  $  4  0   # # 

>   -  #   S )    - 
 0   #

&      
  ! 
)  
U ) 

+ ' 0        #

>   -  #   S )     - 
 0   #
L    ' H '  
U ) 

?   !       N   
# A        #
80  # ! U )  !! 
 ! 3/:60559:(68197383/86(
38A:):3:(6H/:)/+(<:18,H8,6(1
H/:9(8163427 

?   !  

>   -  #   S )     - 
 0   #
&(/*(1(35235,(7$5<,1)250$7,21
  
  
 # 5
 # 5
(109:28*:2
(109:28*

7$
?   
?   

> 
> 
 0
 0
5,(
52
( 3
   ' 
   ' 
) 
) 
/*
80  
0
&(

      
                 
    !  
     !
 (   "
#  $ % " & '  (
*; V   S - :8  ;  
'' S $ - :8
8, PA 
 8929(109:28*:2(286:1<O
,(3(63039(063H((E97413:9
8,W.A 8,
,(34,138+06(9:1(
(64*(3/(60*(286(8;
9(109:28*:2(:;3/((=(13:6
)816:2(,(2  ,(903(238
634272,4<3,(03*(13
(630,39(109:28*:2(
3,(03*(13031(A398H(,286(
9(=(9:;3/((=(13:6
)816:2(,(206,(903(238
2,4<3,(03*(13
*; V   S  - :8   ;  
'' V $ - :8
:9:,4+:1P A X
 8929(109:28*:2(286:1<O
,(3(63039(063H((E97413:9
+:9:,4+:1W.A 

(64*(3/(60*(286(8;
9(109:28*:2(:;3/((=(13
:6)816:2(,(2  
,(903(238634272,4<
3,(03*(13

(630,39(109:28*:2(
3,(03*(13031(A398H(,
286(9(=(9:;3/((=(13:6
)816:2(,(206,(903(238
2,4<3,(03*(13
*; V  - :8   ;  '' V 
$ - :8
4*8, 90,(
,02(8,'

13(,,4539(109:28*:2(3/(,057012:1:3:03(3/(,057
H:3/)8,3:)863(,8:26 6012C8,10,)83:)6

(64*(9(109:28*:2(2(),(06(81(286(9(=(9 H/(1
67*538*6,(689=(38!,02(

90+8,038,7012,02(

0*(286(8;9(109:28*:2(*07+()813:14(2H:3/843
:13(,,453:818,286(,(24)3:81033/(:1=(63:<038,!6
2:6),(3:81.

86((6)0903:81383/(1(A3)816()43:=(286(9(=(9:6
5(,*:33(2H/(190+8,038,7:6,(689=(2012,02(
:6,(689=(238,02(.
Y,02(

13(,,4539(109:28*:2(3/(,057.

07,(64*(9(109:28*:2(H/(13/(,(689=(638W
,02(2(),(06(81(286(9(=(9 

;9(109:28*:2(:6,(64*(25,:8,383/(630,38;3/(
64+6(M4(13)7)9(0)/(*:63,73(636/8492+(5(,;8,*(2
(=(,783/(,207;8,3/(;:,63H((E;8998H:1<:1:3:03:818;
9(109:28*:2(.

((6)0903:81+781(286(9(=(90303:*(H:99+(
5(,*:33(20;3(,)8*59(3:818;81(;499)7)9(H:3/843
90+8,038,78,Y,02(
&(/*(1(35235,(7$5<,1)250$7,21
$7
0$
;
286(8
50$
;3/((=(1
50
(2  
250
38634272,
)2
(1
)2
630,39(109
1)2
,(03*
,1)
286(9(=
,1
)81
,1
2,
$7
$7
5<
$7
$5<
28*:2(3/(
7$5
3(,8:26 
(7$
9(109:28*:
5,(7
8*6,(68
5<
5<
35,
0*(286(
235
:13(,,4
23
2:6
52

5,(
52
( 3

      
                 
    !  
     !
   "
#  $ % " & '  (
* ;   *; V  - 
:8
) " *  + , ,,         
 "       
&   % ;       '        =       0       
 #   ! '  $
.
/(0*(12*(1345203(686(82:;:)03:818,13(,,453:81;8,1=(63:<038,!6
)/8:)(,*./:6:6183(2:13/(5,838)89:16()3:81..'
   %
 0 ' #   # #   # 0  8 +  ; *6 #$       
    #$  ;     # A      ! 0 ' !  
         !    #   9 0 !!'    
0  !! # !'     ! # '  $
    %
 0 ' #   # #   # 0  8 +  ; *6 #$       
    #$  ;     # A      ! 0 ' !  
         !    #   9 0 !!'    
0  !! # !'     ! # '  $ 86(6 3/03 H(,( *:66(2 +()046( 8;
38A:):378,01783/(,,(0681H:99183+(*02(45.03:(1366/8492)813:14(H:3/3/(1(A3)7)9(H/(1
3/(70,(0+9(.
&   %          -   $
.
/(0*(12*(1345203(6(3/826012:*:1<8;;;:)0)766(66*(136./:6:6
183(2:13/(5,838)89:16()3:81..
   %
 6)01C
 ; 0     # ,+9  !    '  # 5   R.   & 9 
       5      # (  R        ! # 
N   0  $
                   
     
    %
 6)01C
&(/*(1(35235,(7$5<,1)250$7,21
, 66

   
 

 '
'

 
  !!'
!!'
8 +
 +  ; *6
 ;
   

!
!
 
  
 
$ 
$ 8
8
3:(1366/84
:(1366/84
   -  
   -  
*(134520
*(13452
3/(5,838)8
/(5,838
 % %
(


    
   
     
     

N   0
N   0
  
  
 

      
                 
    !  
     !
   "
#  $ % " & '  (
 ; 0     # ,+ H:3/)813,0639 :; :6)813,0:12:)03(29  !    ' 
 # 5   R.   & 9        5      # (  R   
     ! # N   0  $
                   
     
     ,       ,      ,  ' ##
(       -   '.&(#
&    
E+  ;   G  '     0         #  ;  ! 
         !  Q3$
4    !!        '     ;  ,+ 0   !   $
;  !! '  !    !    '   #      $      $ 9 
      !! !   #  -!  $
.
/(0*(12*(1345203(666(66*(136./:6:6183(2:13/(5,838)89:16()3:81
..
   %

*6H*6 #    8 +  ; *6 L  $   *!!-  $
  ,    ,  , ' ##
(       -   '.&(K

;   4H * 

4 /   '                    ! 
 
    %

*6H*6 #    8 +  ; *6 L  $   *!!-  $
  ,    ,  , ' ##
(       -   '.&(K

;   4H *  8197:1,*503:(136 012503:(136:1),8668=(, 

4 /   '                    ! 
  8197:1,*503:(136 012503:(136:1),8668=(, %
&   %
; !! '  !    !    '   #      $      $ 9   
    !! !   #  -!      $ $
,       ;4,H;        4 /    !!'   ! 0  # 
  $
&(/*(1(35235,(7$5<,1)250$7,21
 
  !  
  !  
     
    
:1
:1 3/(5,8
/(5,
6 L  
6 L  
 
 
 - 

   
   
   
  
 , 
 ,
( 3
  
  
1(
 4H
 4H
4 /  
 /  
 8197:
8197:
 
 
(/
; !!
 !!
    !
    

      
                 
    !  
     !
    "
#  $ % " & '  (

 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
&(/*(1(35235,(7$5<,1)250$7,21
7
$7
50$
25
)25
1)2
< ,1
5<,
5<
7$5
(7
5,(
523
52
352
35
( 3
1(
(1(
*(1
/*(
(/
(/*
(/
(

      
                 
    !  
     !
   "
#  $ % " & '  (
 
 


 
 
.
/(0*(12*(1345203(6,:*0,7;;:)0)71258:136./:6:6183(2:13/(
5,838)89:16()3:81...
   %
; !  !   0  ' !       ! ,!    ,9    ! ,!  
     ,9    ,!   ,$ ;   +  > = !  !   
,!     +>,     9 ((( 0 '   !   '  ; H,+ # 5 
  R .      5      # (  R   $
   0 '      '  ! #0  $ ; 
#    0 '   # $
 0    '   !   1     0 '    
! $
6  0 '   0  ! #   !   5          
  '    ! 5   $ 
    %
,8<,(66:81;,((64,=:=09  
 :62(;:1(2063/(3:*( ;,8* ,0128*:I03:81383/( ;:,638+6(,=03:818;2:6(06(5,8<,(66:818,
2(03/24(38017)046(.;3/(503:(13/061835,8<,(66(28,2:(2 H:99+()(168,(2033/(3:*(8;
9063)8*59(3(2066(66*(13H/(13/(503:(13H06E18H118338/0=(5,8<,(66(2.03:(136H/8H:99
,()(:=( 0 1(H3,(03*(13H:3/84328)4*(13(25,8<,(66:81H:99+()(168,(2 033/(9063 066(66*(13
203(3/033/(503:(13:6E18H138+(5,8<,(66:81;,((6((30+9(+(98H .
 (168,:1<49(6;8,:*(38(=(13,8<,(66:81012C8,(03/ 1258:136
:3403:81
03(8;,8<,(66:818, (168,:1<
:3403:81
 43)8*(
 8+06(9:1(066(66*(136
0128*:I03:81
 (168,(2
&(/*(1(35235,(7$5<,1)250$7,21
/:6:6183(2
:6183
 ,

! 
! 
 
 +
+
   ! 
! 
 R  
 R  
 
 

 $
 $
  1
  1
0 
0 

  $ 
  $ 
=:=09  
=09  
663/(
3/( 3:*(
3:*(
017)046(.
17)046(.
(3(2
(2 066(66
066(66
00 1(H
H 3,(0
3,(0
3/033/(50
3/033/(50
 (168,:1<
 (168,:1<
403
&
0$
50$

      
                 
    !  
     !
"   "
#  $ % " & '  (
,8<,(66:8128)4*(13(2
 :,6302(M403(066(66*(132(3(,*:1(2+7
)(13,09,(=:(H
,8<,(66(2
 85,8<,(66:81
03(8;906302(M403(066(66*(13H:3/
(=:2(1)(8;185,8<,(66:81
 (168,(2
34272:6)813:1403:81;8,,(0681683/(,
3/012:6(06(5,8<,(66:818,2(03/
03(8;906302(M403(066(66*(13H:3/
(=:2(1)(8;185,8<,(66:81
 (168,(2
 (H013:97*5/8*0
C1815,838)893,(03*(13630,3(25,:8,38
5,8<,(66:81
03(8;906302(M403(066(66*(13H:3/
(=:2(1)(8;185,8<,(66:815,:8,383/(
630,38;1(H013:97*5/8*03,(03*(13
 (168,(2
(03/+(;8,(;:,63066(66*(13H/:9(
8163427
03(8;2(03/
,8<,(66(2
(03/+(3H((102(M403(066(66*(13
=:6:36
03(8;2(03/
,8<,(66(2
(03/8,5,8<,(66:810;3(,01(A3(12(2
986338;8998H453:*(3H88,*8,(
*:66(2066(66*(136 
03(8;906302(M403(066(66*(13H:3/
(=:2(1)(8;185,8<,(66:81
 (168,(2
6022:3:8109,8+4631(66)/()E68;3/(5,:*0,7(1258:13012)(168,:1<2(;:1:3:813/(3:*(38(=(13
010976:6H:99+(,(5(03(2;8,3/(5854903:8146:1<3/(;8998H:1<*82:;:(2*(3/8268; %
0 6:1<3/(:1=(63:<038,066(66*(13:163(023/( )(13,09,(=:(H
+  816:2(,:1<5,8<,(66:818,2(03/412(,01(H013:97*5/8*03,(03*(130601(=(13
)  816:2(,:1<2(03/8,5,8<,(66:810;3(,01(A3(12(2986338;8998H453:*(3H88,*8,(*:66(2
066(66*(136 0601(=(13
2  1(46:1<3/((0,9:(635,8<,(66:81203((:3/(,:1:1=(63:<038,6(38, 6(3.
; !  !   0  ' !       ! ,!    ,9    ! ,!  
     ,9    ,!   ,$ ;   +  > = !  !   
,!     +>,     9 ((( 0 '   !   '  ; H,+ # 5 
  R .      5      # (  R   $
   0 '      '  ! #0  $ ; 
#    0 '   # $
 0    '   !   1     0 '    
! $
&(/*(1(35235,(7$5<,1)250$7,21
7,
,(2
,(2
7,
7,
7,
3
 (168,(
 (168,
0$
25
)2
< ,1
02(M403(06
2(M403(06
8;185,8<,
8;185,8<
$5
,(
0,7(1258:1
,7(1258
4903:8146:1
4903:8146
163(023/(
163(023/
03/412(,0
03/412(,
<,(66:81
<,(66:81 0;
9:(635
(635,8<,(
,8<,
  
  
 0
(1
 ,9 
,9   
  
(1

*
   +>,
 +>,
*(
.    
.    
/*
 
  

(/
#  
#  
&(

      
                 
    !  
     !
   "
#  $ % " & '  (
6  0 '   0  ! #   !   5          
  '    ! 5   $ B2(03/68,5,8<,(66:816/0=(8))4,,(2.
&   %    !     4  !  ! $
@.
/(0*(12*(1345203(6()8120,71258:136./:6:6183(2:13/(5,838)89:1
6()3:81...
   %
K    ##  4
4          1       '#     !          
$ +  !    !    9 4 0 '            0! 0 
 ! 0 = 0     # ! $  0  0 #  0   0  
   !   0 '           !  = 0   ' 
!  K
    %
 =(,099(65816(
/( 5,:*0,7 ,(65816( ,03( H:99 :1)942( +(63 ,(65816( 8;  8*59(3( (65816(     8*59(3(
(65816( 41)81;:,*(2  4  8, 0,3:09 (65816(  . /( 82:;:(2 13(,103:8109 "8,E6/85
7*5/8*0(65816( ,:3(,:0"   /(681--- H:99+(46(2012,(65816(066(66(2+7 
6)01H:3/)813,063CH:3/)813,063(=(,7@2076R?2076 ;8,3/(;:,63@*813/60123/(1(=(,7
-2076R20763/(,(0;3(,.
03:(136 H/8 2:6)813:14( +(;8,( 017 5863,0128*:I03:81 (;;:)0)7 066(66*(136 H:99 +( )816:2(,(2
181,(65812(,6.
   ##  4
4          1       '#     !          
$ +  !    !    9 4 0 '            0! 0 
 ! 0 = 0     # ! $  0  0 #  0   0  
   !   0 '           !  = 0   ' 
!  $ 
&   %    !     4  !  !   F,,   #   
  ! $
?.
/(0*(12*(1345203(610976:6(3/826./:6:6183(2:13/(5,838)89:1
6()3:81..
   %
*   0 '         '$
&(/*(1(35235,(7$5<,1)250$7,21
 
   
  0
  0!
!
0 
 
 
! 
!   =
16(
6( 8;  
;
8*
8*
 .
 . /
---
---
,(
 H:99
H
@2076R?
@2076R?
5863
5863,012
,0

3
  1 
  1 
( 3
 
(
  
  ! 
! 
(
 0 
 0   
    
1(
  
  0
(1
$
$
*(
  
  %
/*
 ! 
 ! 
?.?.

      
                 
    !  
     !
5   "
#  $ % " & '  (
*   0 ' !    4 *   4*  #     
!  !        ! $ 
;       !#N  0 ' 1  ! !    !   !# 
 $
; !     !  0 ' !      +;;  4* ! !    ! 
#   ! 5            '    ! 5   $  0   !   
    0  ' #   0 '     ! $ ,!     !  
 #      0 '      ! $
&    !  0 ' 1 0    ! !    !  ! $
  !  0 ' 1        !     ! $ * !    
    # !    # ## 0 '           0 !$ 8  D    
 !           !# $
; ! ''   !   0 '     ! !     ! 0 !  0 
- 0  (P   #$
; @! !  0 '    1     # !   9 49 ;;9 ;;,9 
F      ! $    #   !# 0  (P   
# 0 ' ! #       #'$ 
; 6F,;  CC  0 ' 1      '  !       
'           !$.          6F,;    
 $     ' !      -!      '    $($ 
; 6F,;  , &    9  3 0   '    !# =   !' 
'0 !      0     !' ! ! $ ; !       # 
!     !  *  / 0 ' 1   !#  $
    %
*   0 '         '$
*   0 ' !    4 *   4*  #     
!  !        ! $ 
;       !#N  0 ' 1  ! !    !   !# 
 $
; !     !    0 ' !      +;;  4* ! !    ! 
#   ! 5            '    ! 5     0   !   
    0  ' #   0 '     ! $ ,!     !  
 #      0 '      ! $;3(, B 2(03/6 8,
5,8<,(66:81/0=(8))4,,(2.
&    !  0 ' 1 0    ! !    !  ! $
; @! !  0 '    1     # !   9 49 ;;9 ;;,9 
F      ! $    #   !# 0  (P   
# 0 ' ! #       #'$ 
&(/*(1(35235,(7$5<,1)250$7,21
 
 
!
!   
  
 D 
D 

 0
0 
! 
!   
!#

0 
0
'
 


 
   
   
   
   
0   ' 
0   '
' ! !
' ! !
  !
  !
   
   
!
!

 
  
 
    
    
35


35
#N
# 
(
   
   
1
 5   
 5   
*(
 0  '
0  '
*
#

  

/*
<,(66:81/0
<,(66:81/0
&   
&   
&(

 @
@

      
                 
    !  
     !
.   "
#  $ % " & '  (
14163,03:;:(298<,01E3(63H:99+(46(238)8*50,(3,(03*(130,*6;8,3:*(38(=(13=0,:0+9(6.
/(  8A 5,858,3:8109 /0I0,26 ,(<,(66:81 *82(9 H:99 +( 46(2 38 066(66 3/( 6:<1:;:)01)( 8;
63,03:;:)03:81;0)38,6813,(03*(132:;;(,(1)(6.
03:(136H/82,858438;3/(63427H:3/843+(:1<(=09403(2;8,H:99+()8413(206181,(65812(,6.
(65816(6 ;,8* 503:(136 0;3(, 3/(7 ,()(:=( 83/(, 013:)01)(, 3,(03*(136 H:99 +( )8413(2 06 181
,(65812(,.
  !  0 ' 1        !     ! $ * !    
    # !    # ## 0 '           0 !$ 8  D    
 ! 0           !#  +(0559:(2$
; ! ''   !   0 '     ! !     ! 0 !  0 
- 0  (P   #$
; 6F,;  CC  0 ' 1      '  !       
'           !$.          6F,;    
 $     ' !      -!      '    $($ 
; 6F,;  , &    9  3 0   '    !# =   !' 
'0 !      0     !' ! ! $ ; !       # 
!     !  *  / 0 ' 1   !#  $
&   %
   !     4  !  !   F,,   #     ! $
&     ! 9      !! !     $
B.
/(0*(12*(1345203(6 13(,:*10976(6./:6:6183(2:13/(5,838)89:16()3:81
.?
   %
K 4  0 '   0 !! -  3 !   !     00 
'    !      " !   ,#  $
/    (P + !! 9   !! '   ' 0   P   #  9  &    
     !!  K
    %
K 4  0 '   0 !! -  3 !   !     00 
'    !      " !       $
 H:99)8124)301010976:6;8,;43:9:3781 012 =(,099,(65816(,03(. 865():;:)63855:1<
,49(6H:99+(<:=(1383/( ;8,3/( O3/(;8998H:1<,49(6*:</3+(46(2;8,8=(,099,(65816(
,03(.
/    (P  + !! 9   !! '   ' 0   P       9  &  
       !!  K
&   %&  #0 -   4  F,,$
&(/*(1(35235,(7$5<,1)250$7,21

   
 
!  
!  0
0
 
   
  
 
 
 6

F,;
F,
' 
  
  
!# 
!# 
 !  
!  
   F,
   F,
!! !
!! ! 

,:*10976
:*1097
 
 0 
0
 " !
 " !
9
  

 
 K
 %
(

 0
0 '
!  
  
H:99)8124)
H:99)8124)
6H:99+(<:=
6H:99+(<:=
03(.
03(.
/ 
/  


      
                 
    !  
     !
3   "
#  $ % " & '  (
-.
/(0*(12*(1345203(6 0*59(:I(0128H(, 816:2(,03:816. /:6:6183(2:1
3/(5,838)89:16()3:81.B.
   %
;    'D#           F# ,!  ,  F,,$
 ! 1    '    0    (P   #     !  
    F,,       #$
/   !       ' -!  !        P   "P$$$
K *         !#        ! 1   0 '         
 $ >       !         $
    %
;    'D#           F# ,!  ,  F,, 2(*8163,03(3/(
(;;:)0)78;9(109:28*:2(8=(,06:1<9(0<(138;:1=(63:<038,!6)/8:)(+06(281 .
/(5,:*0,7010976:6;8,3/(63427:638)8*50,( +(3H((19(109:28*:2(01206:1<9(0<(138;
:1=(63:<038,!6)/8:)(. 8,3/(5,:*0,7(;;:)0)7=0,:0+9( 0/0I0,2,03:8  8;.?9(02:1<38
01:*5,8=(*(13:1*(2:01 ;,8*.*813/6;8,3/()813,890,*38039(063'.*813/6;8,
9(109:28*:2(:6)816:2(,(2)9:1:)0997,(9(=013.
/(6(0664*53:8160,(64558,3(2+7,()(13203054+9:6/(2:1,(9056(2,(;,0)38,7 .
":3/0/0I0,2,03:88;.?;499:1;8,*03:811()(660,7;8,081(6:2(298<,01E3(63H:3/018=(,099
095/08;.38/0=(BL58H(,H:99+(0)/:(=(2H/(1055,8A:*03(97B503:(136/0=(
5,8<,(66(28,2:(2  .
/(60*59(6:I(:1:3:0997H06)09)4903(238(63:*03(3/( =(,099(65816(03(  .
 ! 1    '    0    (P   #     !  
    F,,       #$
/   !  9  !        P   "P   ' ' -!K
K *         !#        ! 1   0 '         
 $
 8;8,*0960*59(6:I()09)4903:81H:99+(281(;8,3/()813,890,*. >       !  
       $
664*:1<3/03L8;503:(136H:99+(986338;8998H45@?503:(136H:99+(,0128*:I(2.
&   %
 !  #    0 4  !   'D#$
  '  -!   1 !  !         0!9     
#        !   $
'.
/(0*(12*(1345203(6 3/(,85:)6./:6:6183(2:13/(5,838)89:16()3:81
.-.
   %
  0 ' !       !  0   !     -!   !! $
&(/*(1(35235,(7$5<,1)250$7,21
  
  
 
2
2(*
2(*8163,
8163
 .
 
(01206:1
0120
03:8  8;
3:8  8
38039(063'
039(0
(9056(2,(;,
(9056(2,
81(6:2(298
6:2(29
1055,8A:*
055,8A:*
3/( =(,09
3/( =(,0
 (P  
(P  
 #
 #
   
  
 
     
   
23
03:81
03:81 H:99
H
+
503:(136
503:(136 H
 %
(
  #
 #
'  
'  -!
-!


  
  

'.
'

      
                 
    !  
     !
(   "
#  $ % " & '  (
    %
  0 ' !       !  0   !     -!   !!  ;8, 3/(
6()8120,7(1258:136.
&   % E  !  0              
     !#     !#$
'.
/(0*(12*(1345203(6030010<(*(13./:6:6183(2:13/(5,838)89:1
6()3:81B..
   %
& 0 '      ' !   F$ ;  0 '   # 
     !     = ! '    $  
    %
& 0 '      ' !  
F 419(66:13(,1095,8)(66(6H:99
+(281(+7030010<(*(138; (9<(1(:13/:6)06( (9<(1( 6H:99+(46(2#
&   %       F 9 =      
   
- #     #9     $
'.
/(0*(12*(1345203(6 (;(,(1)(6./:6:6183(2:13/(5,838)89:16()3:81.
   
O1 9 >1 ;69 L  Y9  $  6        F  !  ! 
0 ,!   ,      !   ,       $      *? 
*  *'N 8 #$  3N    5 $
    %
O1 9 >1 ;69 L  Y9  $  6        F  !  ! 
0 ,!   ,      !   ,       $      *? 
*  *'N 8 #$  3N    5 $
":3I:<86([.:1I01:((2(, 4)E63(:189:E8;;[48:(3,81:<,8
,=:1 071(6012 I4)I*01 11409((3:1<+63,0)3 O 8=.-O+63,0)3&@?@
   %
 (66 (,+,()/38*0<4(,0[(,/8(; ,4*5:66(9+,()/3 04,(99 ;;1(, 
3,0/6(,E(1+9:3 0146/(=6E7  901)7[ (H(688,(012 8:;;:(,./06(
342738=09403((*6:,89:*46 8*50,(2":3/1=(63:<038,!6 /8:)(/(,057;8,3/(,(03*(13
8;(9056(28,(;,0)38,70139( (997*5/8*0.[ 9:1 1)89-O?%BB-.
&   %  !$
&(/*(1(35235,(7$5<,1)250$7,21
  #
 #
9(66:13(,10
66:13(,
99+(46(2
9+(46(2#2
    
   
:6:6183(2
:6:6183(2
   
   
 !  
!  
 
 ,
  5 $
 5 $
 
 $ 
$ 
52
6
6
52
 
 

35

35
 
 
35
8 #$  3N 
8 #$  
3
:1I01:
:1I01:
2 I4)I*0
2 I4)I*0
%
(
,+,()/3
+,()/3
(,E(1+9:
(,E(1+
38=09403
38=09403
(9056(28,
(9056(28,


      
                 
    !  
     !
"   "
#  $ % " & '  (
'.
55(12:)(6.
    %  $( 6F,;  CC  C 
& %      
&(/*(1(35235,(7$5<,1)250$7,21

      
                 
    !  
     !
   "
#  $    %!  &
     
        
          
                !       
 "         
 # $
    %
   
  &%

%
'()*+
   
           
              
    !  " #$ " 
          
        #
&(/*(1(35235,(7
 
 
 
 
  ! 
 !
 
 

  
 
  
  
(7$5<,1)250$7,21
(7
(7
35
35

      
                 
    !  
     !
    "
#  $    %!  &
,
-./0.120.134'2/3.53-.3426.(5711.*,-)5)5173.2)13-.3426 713/83197(0/3)71
/:*.,
   
7*.)13426
 /0.
22(.55/12.*.'-71. 40:.(
' (  
  ) 
*   + 
 , -   ./
  
3+ 
4  
 (    
*! ( 
  
* 
  ) 
*   + 
 , -   ./
  
3+ 
4  
 (    
)  
8 
   
..''.12);,97(
*78/* /99)*)/3. 8713/83
)197(0/3)71 
  9 
  )  
*   + 
 , -   ./
  
3+ 
4  
 1:  
  
 
9  
)   #( 
 1     9  
    %
*    *! (   * 
=  
%  9!  = (
  ) 
*   + 
 , -  > ./
   
3+  
 
&(/
  9
  9
  )
  )

/*(1(35235,(7$5<
   
  
  )
  )
*   
*  
 
 , 
,


$5
5,(
23
1(
1(
1(
1(
 % %
(
 *! 
 *! 
5<,1)250$7,21
$7
/

25
25
< ,1
5<,
5<
5
52
(/*

      
                 
    !  
     !
   "
#  $    %!  &
4   
 (   
     %
)  8    
3    8  % ?      7 !       %# 4# 
*!  3      !  '
 1:  4    
)   #( 
 1     9  
   
8       
+4@  
' ( 8   =  
% 
  ) 
2"   %#
  7 =. B ,&
  
 
3+ 
4 
&  %
   ! $
=  %       (    +4@   C )$
,
-./0.120.134'2/3.53-.1/0.798.13(/**/:7(/37(6).5 /1273-.(0.2)8/*/12<7(3.8-1)8/*
2.'/(30.135 /12<7()153)343)715
   %
&(/*(1(35235,(7$5<,1)250$7,21

  

 
 
2"
2
(7
35
5,(

%
1(
$
  
  
-.
-. /0
/0.120
.12
2.'/
2.'/
 
 
&

      
                 
    !  
     !
1   "
#  $    %!  &
     %
)# 6  *!     )6*
 
 
&(/*(1(35235,(7$5<,1)250$7,21
235
3
(
1(
(1
(1
*(1
/*(
/*
(/*
&(
&

      
                 
    !  
     !
   "
#  $    %!  &
&   %
9    7 ! (   /     (   L   L  
!  $

 
 
 
 
@,
-. /0.120.13 4'2/3.2 3-. /8AB(7412 /12 (/3)71/*.,  -)5 )5 173.2 )1 3-. 5617'5)5
/8AB(7412/12/3)71/*. ,
   %
/8AB(7412/12/3)71/*.
M$ )    =:          !  ! . ! # =:7 
   1& !     JC7  ,N JC7  2$    !       ! 
!    *7    ! !       *  " ! !   *   ! 
.    9 7  ,$  3     ! .  !     ! ! $ )   
            !  ! . !     =:    =:
7  2   2& #( !      // 7  2$      !      (I# 
!     "O  ! .  $ )    ! ))    =:   =:7 
          L1 # # .  !   O    (  !  O 
 :( 7  2M
     %
/8AB(7412/12/3)71/*.
/
/8AB(741
B(74
A
/*. 
/*. ,
/*.
/*.
=:
=:  
 
 
  
 
   !
  !
 9 7
9 7  

   
  

 2   2& #
 2   2& 
! 
!  


    
   
:( 
:( 
5<,1)250$7,21


50
1)2
5<
$5<
7$5
35,(

      
                 
    !  
     !
"   "
#  $    %!  &
M$ )    =:          !  ! . !     
# =:  JC  27    1& !   $ )    !    ! 
#  ?# *!  *  ?**   O$ 9 !   O    *       *7 
  !  O   *$ 9       !  . $,       3 . 
$"   $ 9          1 # # .   (  !  O           
  # # .  !  1O7  !   ,O7    (  !   O$ 
 :( 7  &$ )               !  ! . !   
  # =:    =:7      !     P/7  2$ )  & 
  ! .  . #(   !   7      !      (I# 
!     1O .   *   *$ 9             1 # # . 
 !  O    (  !   O7    O7   O  (  ! 
 O  P/7  2$$$$
&   %
@!  #($
,
-./0.120.134'2/3.28(..1)1B-/5.,-)5)5173.2)15617'5)58(..1)1B-/5. /12)1
5.83)715C,,, 793-.'(73787*
   %
 . (    !    ( .  2  !      /      9(
       % $  L(   . (    !  
!! #           $  -        . ( A . , 
         $  4(      (          -   
   .            L  !   ( !  (    . !  Q 
!!(R     L( !    $
8        !   (   !   #.   (   ! !    
  / $ 9         ( !! #     !  7  
 #+!     8 (          N1 AA  ( 3):$ ) ! .  
    #     8    7 #    #+!     8    8 
(       . ( !($ 9   L  !   ( ! ! 7 .   ( 
#     !   (         7 . !#   
!!            8    3): 7   (     !   
(    /              !  N  !7 1     
  ( ( $  )  !      #(   (  7   ( !  AM  
     %
 . (    !    ( .  2  !      /      
9(        % $  L(   . (    !  
!! #           $    ! (       -        
. ( A . ,          $  4(      (      
    -      .         #    L  !   ( ! 
    L( !    $ 
           !     (   !      A (  
  /      7 ( . ( !       $  4(     
&(/*(1(35235,(7$5<,1)250$7,21
& & 
#
#

.
.
 !
 !
7'5)5
5)5 8(..
8(
 !    
!    

 
 
   
   
 
  (
(
 L L  !
 ! 
!   
!   
  
 
!
!
  

   
   
 8
8 
 
 (
( 

!

 
 
 (
 (
   
   
 
 
   
   
 
$  )  !
$  )  !
 %
 %
*(
.
.
(
( 

 
   

!! # 
!! # 
.
.
( 
 

 
 

      
                 
    !  
     !
,   "
#  $    %!  &
 (          !    (  # $  8  (    
!       !( !         $ 
9       (         *#.     ( !! #   
  !   ! 7   #+!     8 (      $ ) ! 
.      #     8  #+! 7 #    #+!     8    8 
(       . ( !($ 
9   L  !   ( ! ! 7 .   ( #     !   (     
    7 . !#   !!           !   
 :S4   '      8 7   (       ! (    !   
(    /  (    2 .C    / $ )         (  
     ! ( C      ( C$ )     ( C   ( 7 1   
    ( ( $ )  #     #(   (  7   
( !  A$
4#        N1 AA  ( 3):   ( (         
  !     !  !$ 9     N1 AA  ( 3):   !   
       !      $ ) #(7           7    
!   #.7           87  87  87  8 7  8 7 -  $
3  7          !     (    . ( !  7    
     ( C          #.    2 .C    / $
 
8  L( !7  #           T# U  V 
 !     ! !       / $
&   %
     !  A    !               $ -  
  . ( !           

      7   +   !      

         (    .  

I  +!    (  !   !

)       !     !     )# U         
(  $ 
?,
-./0.120.134'2/3.2(./30.13-/5.173.2)15617'5)53/:*.9773173.  )B4(. 
/125.83)71C,,,793-.'(73787*
  %
9          ! (    / 7 (  +     (. 
  /     8  1 M 
&(/*
$
-.
-./0.
/0
/1
/1
 
*(1
  


1(35235,(7
  
    
  
 !
 !
    
   
7   +
7   +
  (   
  ( 
    
   
7$5<,1)250$7,21

  
 
  
  
 ( 
( 
1
  
 
 7
 7  

 
 
  
 
  ( 3):
  ( 3)
   
   
7  8 7
8 7  

  
  . 
 
 2 .C 
2 .C 
7$5
(7$
(1(
/*(

      
                 
    !  
     !
2   "
#  $    %!  &
    %
9          ! (    / 7 (  +     (. 
  /     8  @2/657    !    A        
! !#  !     %!!  $,   $2M
&   %
9   ! /     7  !        %  -     #7  
     / $
D,
-. /0.120.13 4'2/3.2 (./30.13 -/5. 173.2 )1 5617'5)5 /12 5.83)71 C,,, /12 79 3-.
'(73787*
   %
 
     %
 
 
 
&   %
C,
-. /0.120.13 4'2/3.2 3-. '(7'-6*/;)5 79 3407( *65)5 5612(70. 173.2 )1 5617'5)5 /12 )1
5.83)71,,793-.'(73787*
   %
9              #     ! !+   !   
A#  ( .        ,             
     $ :  #   ( I        $ 
9                 ! 7  ! . #    ! (     
  -     .   8 7  7 17 2             
$  9 . (  (   - ! '  $   %!!+  $"$
    %
)  ! # ! (   9   (  !   .         # (   
   7 !  7 ! !         W '  9   (  !   (   
9              .   W $ + @=7     /7 
!! !        (               
&(/*(1(3523
3-. '(7'-6
'(7'-
'(73787*
(73787*
  
  
 . 
 . 

 

  
   
  
 
  
 
$
$ 9 .
9 
  
   
 

&(
 !
 !
35,(7$5<,1)250$7,21
/12
/1
79
79 3-.
3-
)2
1)2
,1
5<
$5<
7$5
(7$
(7$
235

      
                 
    !  
     !
&   "
#  $    %!  &
  . #   )6    (      !! !    !! # ( 
   : % $
&   %
9  ! #    ! !        9      $
+,
-. /0.120.13 4'2/3.2 '(7'-6*/;)5 97( 3-(70:7.0:7*)50 173.2 )1 5617'5)5 3(./30.13
'-/5. 5.83)71,,?793-.'(73787*
  
        . # ! ! ! Q  7 %%RR  , >  
     $  .     C      (  (  #7   
       (  (  # L   C . ! (       (  (  
 7   !  .   %%   7             # 7  
    .    . !   .    A# 6  ;     C!  )=*  
        (  $
    %
   C      (  (  #   C     + !        
  (  (  # L  C           .   C    
  (  (  # L   C . ! (       (  (    . 
# ! ! ! Q%%R  , >       $  ) %%  
 7     .    . !   .    A# 6  ;     
C!  )    /    )=*          (  $ 
&   %
9    ! !+   ! .  C     (  (  #$
, -./0.120.13/22.2'(.8)5)71713-.)1)3)/3)71798(7557>.(3(./30.13,-)5)5173.2)13-.
5617'5)5 3/:*.  /12 5.83)71 C,,, 79 3-. '(73787*  (755 7>.( 97( '/3).135 )1 3-.
)1>.53)B/37(58-7)8.(071*6 
  %
3  !  %  -   .    .        #     +   !  
 $ 9  .    . (   7 !  # 7   # ## 
  .!$ 
    %
3  !  %  -   M$$ -. 0/;)040 24(/3)71 :.3E..1 */53 2/6 79 */53 868*. 79
3(./30.13)1(0/129)(53*.1/*)270)2.868*.)5E..A5 M$ 9  .    M
&   %
9  +        #      %  -       7  . !   
 #     +   %  -  $
&(/*(1(35235,(7$5<,1)250$7,21
3
%RR  , >
 , > 
>

#7 
#7 

  
  
  
  

( 
 
   #
   #
   
   C
C
 
   

  
  



 
 

 .  
 .  
    
    
C     
C    
)5)71
)5)71 71
71 3-
3-
1
2 5.83)71
5.83)7
.(071
.(0
 -  
 
  
  .
. 
  %
 %
/*
!
! 
3(./30.13)
(./30.13)
 
 
&

      
                 
    !  
     !
   "
#  $    %!  &
, 9    !   #   )! 4+    *#.$  9  
     !7 (         "    2$    !   
  %
%# !       !  L   ( ! !   (          
 !!           (     !              
 !  $  )  # !      #(   (  7   ( !  A 
!      / $  % !  !   . #.   !  L   ( !  
.   #( (    . ( !  !     !       !# 
               !  $ 9 ##    (   ! 
 L   ( !    #( (    . ( !  !     !   
  !     !    .       #.  .     # 
 3):    8      N1 ANA $  ) ! .      #    
 8       .       (/   3):     #(7 
!   !      #+!          87  8    8 ( 
      . ( !($  9 !   .   #.  !   !  
 (  !   !   7      (    . !  ( ! 
A   !       *L *$
    %
% !  !   . #.   !  L   ( !    !# 
               !  $ 
9       (         *#.     ( !! #   
  !   ! 7   #+!     8 (      $ ) ! 
.      #     8  #+! 7 #    #+!     8    8 
(       . ( !($ 
9   L  !   ( ! ! 7 .   ( #     !   (     
    7 . !#   !!           !   
 :S4   '      8 7   (       ! (    !   
(    /  (    2 .C    / $ )         (  
     ! ( C      ( C$ )     ( C   ( 7 1   
    ( ( $ )  #     #(   (  7   
( !  A$
4#        N1 AA  ( 3):   ( (         
  !     !  !$ 9     N1 AA  ( 3):   !   
       !      $ ) #(7           7 7    
!   #.7           87  87  8 7  8 7  8 7 -  $
3  7          !     (    . ( !  7    
     ( C          #.    2 .C    / $
 
 
 
 
3   7 !     !    $
&(/*(1(35235,(7$5<,1)250$7,21
  
#
#
 !
 !
!  
  
 
 #
#
#
#   

  
   
  
 
 8 
8
 
 ! 
!
 
  . 
 . !

  L 
 L
  
  *#.
*#.
  
  
 8

! 7
 7 #
#

  
  (
(
 
 

 8
 8 

 
 2 .
.
C C   
  
( $ 
( 
  
  
   
   
 
 
  
 
 #.7 
#.7 
  7
  7   
    
   
&

      
                 
    !  
     !
   "
#  $    %!  &
&   
9   !  A    !              7 
, -./0.120.13/22.2''.12);,C#.1/*)270)2.(.B1/186)5A)1)0)5/3)71*/1.;
3.(()37().5 $,-)5)5173.2)13-.5617'5)518*45)71 ()3.()/ )13/:*.9773173. 
/125.83)715+,<,@<,793-.'(73787*
& %
9 !!+      *C     !   =  % 
.   !!   .  ) $ 
, -./0.120.134'2/3.234267'4*/3)7118*45)71 ()3.()/,-)5)5173.2)13-.5617'5)5/12
)13-.'(73787*5.83)71+,,
   %

 .    ! #     : CU  !   Q R X 
 #+!     8 (          N1 ANA     
( 3): Y$ ) ! .      #     8  #+!  
    7 #    #+!     8    8 (       
. ( !(M

M3    ( !   3 -  

:#  #   !# !  !        !$ 
         !         7    
   !   !  %!!  $,   $2$ 9 !! #   
! !   !    + (

M !  

%          +   .  3 -7 #   #   
#  7      !7     !    
     !   !  %!!  $,   $2

%            !     !       
 !   !  %!!  $,   $2

% !  

:#         #  !    C$  

%   (      (   . C   !    . 
       !   !  %!!  $,   $2

%          .   ! $

%   (   (  ! !   C    +! $   
!  %!! $,   $2M
&(/*(1(35235,(7$5<,1)250$7,21
  % 
% 

3.2)13-.56
3.2)13-.5
CU  !
CU  !
 
    
 
#
#  
 
  
 8 
8
 -
 -  

 
# 
# !
!
 
 

 
%
   
   
     
    
7   
7  
     
    


     
    

 !
 
 !  
!  

:

      
                 
    !  
     !
    "
#  $    %!  &
     %

 .    ! #     : CU  !   Q R X 
 #+!     8 (      Y$ ) ! .      
#     8  #+!      7 #    #+!    
 8    8 (       . ( !(M

M3    ( !   3 -  

:# 3E7 #   !# ! 3.535 !        
!$          !         7  
     !   !  %!!  $,   $2$ 9 !! # 
  ! !   !    + (

M !  

%          +   .  3 -7 #   #   
#  7      !7     !    
     !   !  %!!  $,   $2

%         7(5'.(0    ! /1297(C2/65/93.(
.1279534262(4B3-.(/'6   !  %!!  $,   $2

% !  

:#         #  !    C$  

%   (      (   . C   !  97(C2/65
/93.(.1279534262(4B3-.(/'6   !  %!!  $,   $2

%          .   ! $

%   (   (  ! !   C    +! $   
!  %!!  $,   $2M
&   %
   /1/*65)5:.870.57'3)71/*      7          !       
 $
    (. !      !   # '(.B1/1863.535 (    $
       2  .   !  A   (  7     !        . 
   * $
&(/*(1(35235,(7$5<,1)250$7,21
 

7 
7 
 !!
 !! #
   #
   #
!  
! 
$,   $2
   $2
 ! 
 

  $,
 
   #
   
  . C
 . 
6   !
  !
  .
  
(  
(  !
!
%!!
%!!
0.5
0.5 7'3)71
7'3)7
. ! 
. ! 
  
  
  2
 2
   *
   *

      
                 
    !  
     !
   "
#  $    %!  &
@, -. /0.120.13 4'2/3.234267'4*/3)71;8*45)71 ()3.()/,-)5)5 173.2)13-.5617'5)5
/12)13-.'(73787*5.83)71+,,
 
     ( #        +! !     A#    
       $ )  7 !    A# !        !!     
     !     .$
   
     ( #     +!   !  Z   L   A#   
!!       $
    %
/,
   ! . 1 .C !      / $
:,
%    +!    1 .C !      / $
& '  
     ! (     ! .  # !   !   !  +!  
!$ 9   !        !$
, -./0.120.134'2/3.21>.53)B/37(!58-7)8.3-.(/'6,-)5)5173.2)13-.5617'5)5/12)13-.
'(73787*5.83)71,,,
  %

   (

*+ (

 (

' (

3(
    %
   ( (     
!LL $ $ $CL LLL L!8 3$![  \ 1,1
!LL $ $ $CL
*+ (    # 
!LL $ $ $CL LLL L!8 3$![  \ ,
 ( )I       L  
!LL $ $ $CL LLL L!8 3$![  \2 ""
' (  # 
!LL $ $ $CL LLL L!8 3$![  \&"
3(       ( 
!LL $ $ $CL LLL L!8 3$![  \1 1
&(/*(1(35235,(7$5<,1)250$7,21
 
  
 
 $
 $
 !
 !
'6,-)5)5
'6,-)5)5
   
 
$ $CL
$ $CL
$ $
$ 
(    #
   #
 $ 
 $ 
(
( )
 )
!LL 
!LL 
 

      
                 
    !  
     !
1   "
#  $    %!  &
3(   L            )I    ) 
     !(     ! # (  
    %
! ! . ( ! #   )# ]    ($
& '  %
9  ! # )# L  . .( C       %  -7  !!  !    $
?, -./0.120.134'2/3.2/:*./12/:*.8-.24*.7955.550.135 
  %
&(/*(1(35235,(7$5<,1)250$7,21

      
                 
    !  
     !
   "
#  $    %!  &
/:*.%
8-.24*.79342655.550.135
(78.24(.
8(..1)1B<
/5.*)1.
C
/65 
 68*.
/6@C
>.(6 68*./6
F  2/65
 68*.5@/6
>.(6?2/65
93.( 68*./6

FD2/6597(3-.
9)(53?0713-5/12
3-.1 .>.(6 + 2/65
3(./30.13
)58713)14/3)71
 7**7E4'97(
'/3).135/93.(
 7**7E4'97(171 
'/3).135
) L+  
G
   !    
G
 =  !   4# 
G
  
)  
   
)+ 
 )) 
G
   !   !
G
  
  
   C ' 
  
G
    91
G
  4 '
G
 !        ( ! !  
"
G
4    !# ?   ' ! 
 4 ?' !   
G
G
G
6 ,
G
G
G
 -  . 82
G
G
G
G
G
    &
G
G
G
G
G
9    2
G
 9  3-   
G
G
G
G
G
-    L      
G
G
G@
G@
8( 
   
   

G
G
G@
%  
  
 !   
 !  
G
G
G
%# 4#
G
G
G
G
G
G
G
*  : !/ 
G
G
9   3 L 9    % 
G?
       L 
G
G
G
G
 +  ,
G
G
G
G
G
 7**7
 7*
'/3
'/3
,2
7,2
,2
$7,
$7
$7
$7
$7
0$
50
5
$
50
50
)250
5
)2
)2
)2
)2
1)
< ,
5<
$5
$5
$5
$5
7$5
5,(
,
5,(7
,(7
G
7
(7
5,(7
35,
35,
5,
G
5,
5,
5,
35,
23
23
235
235
G
35
23
23
523
523
23
23
G
23
23
23
23
23
23
35
352
352
G
52
352
35
( 35
35
G
35
35
35
35
3
1(3

3
( 3
1(
  
(1(
*(
 !  
/*(1
(/*

/*
&(/
 !/
(/
&(
 L 9
&(
&

      
                 
    !  
     !
"   "
#  $    %!  &
 9L*)   C7 7 (    
!#&
GC
G+
G+
9 
 
  
  
  &
G
G+
*!   
G+
  3 ## 
G+
G
G
?# ##
G
G
<   
G
G

G
-   . %!  - ! 1
G@
8!   
G
  
G
G
 .       = # #     =  !   . ( A   # #  3    +  7  
   9L( *)   L( ! $  
 )) 7 !   7 8:7 (  C   7       7  #($
  C '                 L  \  1 >   . QCR L ,      
Q LRN    7       ! ( $2$      (   /  (  
.    (  .7 . #      C 7 &,"7 C7 &&$
1    9     ( 9   97     ( 9   997 %  7 #  J( 3 $
   4 '  !    (     $
" 8        !   (   !   #.   (   ! !      / $ 9     
    ( !! #     !  7   #+!     8 (         
 N1 AA  ( 3):$ ) ! .      #     8    7 #   
 #+!     8    8 (       . ( !($ 9   L  !   ( ! 7 . 
  ( #     !   (         7 . !#   !!  
          8    3): 7   ( (     !   (    /    
          !  $  ) !7 1       ( ( $ )      
#(   (  7   ( !  A$  
,6   .7      7 (   !7  !7  !$
2   ! (        -  .   (       *- 7    (7   7  67 . (    
 J-    . 7 (   !    %= 7 (   !     % 7  !  $
&       ! 7 ( 7  7 ! !  7  7  7   ((7 C ! !7 %97 
%97   7 !  7  7 (     7   8:$
) L(      7    (  !   . ,  (    7 8 7    
     ( !     7 8 $ 
 -     3     (    3 -          (      ( 
  7    # .  # !  !       9  !    ( !   
. 1  !         7     !    ( !   .  1   !    
     $ 9 !     #     )#   #       
!   #$ % ! . ( .      ! (  . (   (  
! !   !  C    +! $   !  (  %!!+  $,   $2$
  8   !!      2    .         3 -      # ! 
   !  (  %!!+  $,   $2$ )      A ! 7  #  
$5
$5
$5
$5
$5
$5
 A   
 A 
     
     
  
     L 
  L 
$2$
$2  
 
 C 7 &,"
C 7 &,"
35
  
  
 
 
!  
  

  !  
 !  


 . 
. 
8 (
8 (    
   

!   (
   (
 8 
 8 

  !  
 

 7   
7    (
7    
7    
  
    - 
  - 
 . 
. 
 
   
   ! 
! 
  7 ! 
 7 ! 
L(
L(
     ( 
     ( 
 
 
&(


  7 
  7 
. 
 


50$7,21
2
7,2
7,2
,2
$7
$7,2
$7,2
G
7,2
,2
$7,2
0$7
0$7
$7
$7
$7
$7
$7
50$
50$
0$
50
5
25
250
50
50
50
50
5
)2
)25
)25
G
5
25
)25
$5<,1)2

      
                 
    !  
     !
,   "
#  $    %!  &
     . 3 -         (      (      #   !  
(  %!!+  $,   $2$ 
% !   (   (  ! !   C    +! $ 
1%  2  !        $
%# # . (   2  !           .!$
"9    L            68*.%/6@C/127  .   $
, +     ! !7 !  7  !     $  
+        (    (7    8  8   8    #  $ 
29      9:7 97 91  !    (L      $
& 9 .  L*)   ( !   # "   ^ ,  !   "              # & 
^   $     . ! !   ! .  #       # # .  
#   ! # $  9 L*)        ( !      .!   ! .  
      !     !$ 
    3 ##    !         +  !      #7 .#    
$    #    %  - #   !    #             
!  $
  . (   .   #      !       # ## # &   ^    
    ,O    ! #         .!  !  !  _         
    !    # !    *L *  ( 7 . #    7  .     . 
(  $
    . (   .   #      !       # ## # "   ^ ,    
   ,O    ! #         .!  !  !  _             
!    # !    *L *  ( 7 . #    7  .     . ( 
 $
 <  . (   L(        8     1 Q 8R  ^, 7     
    ^, $
 1-    . !   ( !     A     !   .    
   *$ 9 (    . !    ( !    2        * #  . (  $ 
  8!     8   $
 
 

 
 
 
 2   )   9    *) .   . 1             7    9    *)     #   
( !      $
&(/*(1(35235
    
   
$5<,1)250$7,21
 
 
.  
.
#   
#   
 
 

   ^
 ^  
 

 
 
   

.   
   
 "   ^ ,
 "   ^ ,
     
   
77  
 .
. 
 1 Q 8R
8R
 
 ! 

     
  
7$5
(7$
(7$
,(7
5,(
5,(
35

      
                 
    !  
     !
2   "
#  $    %!  &
/:*.%
8-.24*. 79 53426 /55.550.135 97( '/3).135 E)3- 8(7557>.( 71 *.1/*)270)2. /93.(
'(7B(.55)71)1)1>.53)B/37(H58-7)8.(0
(78.24(.
 68*.
/6@C
>.(6 68*.
/6F2/65
 68*.5@
/6
>.(6+2/65
93.( 68*.
/6
3(./30.13
)58713)14/3)71
 7**7E4'97(
'/3).135/93.(

 7**7E4'97(
171
3)
3 
4    !# ?   ' ! 
 4 ?' !   
G
G
6 
G
G
 -  .  
G
G
G
G
    
G
G
G
G
 9   3 -1
G
G
-    L       

G
8( 
   
  

G
G
%# 4#"
G
G
G
G
G"
9   3 L9    % ,
G
*  : !/ 
G
G
       L  
G
G
G
G
 9L*)   C7 7 (    
!#
G
G2
9 
 
  
  
  
G
*!   
G
  3 ##&
G
G
G
?# ##
G
G
6   .7 (   !7  !7  !$
     ! (        -  .   (       *- 7    (7   7  67 . (    
J-    . 7 (   !    %= 7 (   !     % 7  !  $ 
       ! 7 ( 7  7 ! !  7  7  7   ((7 C ! !7 %9 
 '?97 %9  '97   7 !  7  7 (     7     $
1 8   !!      2    .         3 -      # ! 
   !  (  %!!+  $,   $2 )      A ! 7  #  
     . 3 -         (      (      #   !  
(  %!!+  $,   $2$
% !   (   (  ! !   C    +! $
"%# # . (    !       .!$
,9   L9          8  7 17 27  7  .  $
&(/*(1(35235,(7$5<,1)250$7,21
 7
 7
171
171
)
7,
$7
0$7
50
2 0
25
2
G
)2
G
1)
,1
,1
,1
,1
,1
5<
$5
G
$5
$5
$5
(7$
(7
(7
(7$
(7
G
,(
5 (
G
5,
35
35
35
35
5235
 
 
52
52
52
52
3
#&
(
1
(
 .
 .
 (   
  

J-    .
J-    
  
 
 '?97 
 '?97 
1 8 
8 




      
                 
    !  
     !
&   "
#  $    %!  &
2 9 .  L   *)      &   ^       . ! !   ! .  #   
     # # .  #   ! # $  9 L*)        ( !   
   .!   ! .        !     !$ 
&   3 ##    !         +  !      #7 .#    
$
 . (   .   #      !       # ## # &   ^    
    ,O    ! #         .!  !  !  _         
    !    # !    *L *  ( 7 . #    7  .     . 
(  $
  . (   .   #   9 L*)    # ## # &   ^        ,O 
   ! #         .!  !  !  _             !    # 
!    *L *  ( 7 . #    7  .     . (  $
&(/*(1(35235,(7$5<,1)250$7,21
O
O
 #
 #

      
                 
    !  
     !
    "
#  $    %!  &
    (     ")%
/:*.%
8-.24*.79342655.550.135C2/65I868*. 
(78.24(.
8(..1)1B<
/5.*)1.C2/65 
>.(6 68*./6
F2/65
 68*.
/6@C
 68*.5@/6
>.(6?2/65
93.( 68*./6

FD2/6597(3-.
9)(53?0713-5/12
3(./30.13
)58713)14/3)71
 7**7E4'97(
'/3).135/93.(
 7**7E4'97(171 
'/3).135
) L+  
G
   !    
G
 =  !   4# 
G
  )     
)+  )) 
G
   !   !
G
  
  
   C '   
G
  4 '1
G
 !        ( ! 
!  
G
4    !# ?   
' !  4 ?' !   

G
G
G
6 "
G
G
G
 -  . 8,
G
G
G+
G
G
    2
G
G
G+
G
G
9    ,
G
 
9 
 3- 
 
G
G
G
G
G
       
( 
   
)     
G
G
G
G
%  
   !  
  !  
G
G
G
%# 4#
G
G
G
G
G
G@
G@
*  : !/ 
G
G
9   3 L 9    
% 
G
5235,(7$5<,1)250$7,21
'/
 7**7E
 7**7E
'/3).1
'/3).1
0 7,
0$
50
50
50
50
250
25
2
)2
1 2
,1
<
$5
7$
7$
7$
7$
(7$
235
35,(
5,(
,(
235 (
52
52
523
23
G
3
23
52
523
352
352
G
52
G
52
52
52
52
352
52
35
35
G
35
35
( 3
( 3
G
3
(
1(

 3- 
(1(
(1
*(1
   
/*(

(/*
/*
  
(1
&(/
  
&(
  
(/*
&
%#
&

      
                 
    !  
     !
    "
#  $    %!  &
(78.24(.
8(..1)1B<
/5.*)1.C2/65 
>.(6 68*./6
F2/65
 68*.
/6@C
 68*.5@/6
>.(6?2/65
93.( 68*./6

FD2/6597(3-.
9)(53?0713-5/12
3(./30.13
)58713)14/3)71
 7**7E4'97(
'/3).135/93.(
 7**7E4'97(171 
'/3).135
     
  L 
G
G
G
G
 +  "
G
G
G
G
G
 9L*) 
  
C7 
7 
(    !#2
GD
GC
GC
9      
  2
G
GC
*!   
GC
  3 ##&
GC
G
G
?# ##
G
G
<   
G
G
G
-   . - !
G/
G:
8!   
G 1
  
G
G
 .       = # #     =  !   . ( A   # #  3    +  7  
   9L( *)   L( ! $  
 )) 7 !   7 8:7 (  C   7       7  #($
  C '                 L  \  1 >   . QCR L ,      
Q LRN    7       ! ( $2$      (   /  (  
.    (  .7 . #      C 7 &,"7 C7 &&$
1   4 '  !    (     $
 *!#      :S4   '    !!            8 
   7  (    .     ( C    !        ! (7 !( (  
  /              !  7 (    2 .C    / $ ) ! .     
 #     87 #    #+!      8    8  !($ % 7  !!   
   ( 3):    !     !  !  ( (       7  #($ )    
          !   #.7           87  87  8 7  8 7  8 7 
-  $ )      ( C    ( 7 1  7       ( ( $ )  #   
  #(   (  7   ( !  A$ 
"6   .7      7 (   !7  !7  !$
&(/*(1(35
35
35
= # # 
 # # 
  
  
 7 8:
 7 8:
   
     
  
 7
 7 

 (  .
 (  .
 '  !  
 ! 
#



 
 
7 
7 
  /  
  /  
 #
#  
 
 
 
   
   
(7$5<,1)250$7,21
$7,
7,
0$7
0$7
$7
0 7
50
50
50$
0$
GC
0$
50
)25
25
25
1)2
1)2
)2
1 2
,1
,1)
1)
1)
1
,1
< ,1
,1
5<
<
7$
7$
7$
7$5
$5
G:
5<
7$
(7
(7$
7$
7$
7$
7$
7$
7$
(7$
,(7
,(7
(7
(7
(7
(7
(7
,(
,(
,(
35235,(

      
                 
    !  
     !
     "
#  $    %!  &
,   ! (        -  .   (       *- 7    (7   7  67 . (    
 J-    . 7 (   !    %= 7 (   !     % 7  !  $
2       ! 7 ( 7  7 ! !  7  7  7   ((7 C ! !7 %97 
%97   7 !  7  (     7   8:$
&) L(      7    (  !   . ,  (    7 8 7      
   ( !     7 8 $ 
 -     3     (    3 -          (      ( 
  7    # .  # !  !       9  !    ( !   
. 1  !         7     !    ( !   .  1   !    
     $ 9 !     #     )#   #       
!   #$ % ! . ( .      ! (  . (   (  
! !   !  C    +! $   !  (  %!!  $,   $2$
 8   !!      2    .         3 -      # .  
!    !  (  %!!  $,   $2$ )      A ! 7  
#       . 3 -         (      (      #   
!  (  %!!  $,   $2$ 
 % !   (   (  ! !   C    +! $ 
%  2  !        $
1%# # . (   2  !           .!$
9    L         7     !  %  %7   68*. % /6 @C /12 7  . 
  $
" +     ! !7 !  7  !     $  
+        (    (7    8  8   8    #  $ 
,9      9:7 97 91  !    (L      $ 
2 9 .  L*)   ( !   # "   ^ ,  !   "              # & 
^   $     . ! !   ! .  #       # # .  
#   ! # $  9 L*)        ( !      .!   ! .  
      !     !$ 
&   3 ##    !         +  !      #7 .#    
$    #    %  - #   !    #             
!  $
  . (   .   #      !       # ## # &   ^    
    ,O    ! #         .!  !  !  _         
    !    # !    *L *  ( 7 . #    7  .     . 
(  $
   . (   .   #      !       # ## # "   ^ ,    
   ,O    ! #         .!  !  !  _             
!    # !    *L *  ( 7 . #    7  .     . ( 
 $
  <  . (   L(      Q 8R  ^, 7    1 Q 8R  ^, 7    " 
Q ,8R  ^, 7    2 Q &8R  ^, 7         ^, $ 
   @ (    . ( !          . ( (           #.  
  . 2 .C    / $
 ( @ (    . ( !     A     !   .       *$ 9 
(    . !    ( !    2        * #  . (  $ 
 1 8!     8   $            ! (    / 7 (  +     (. 
  /     8  1 7    !    A        ! 
!#  !  $
 
 
 
 
 
 
 
 
 
 
&(/*
/*(1(35235,(7$5<,1)250$7,21
 
 
#
# .  
. 
7 
7 
 
 # 
#  
 
@
@ C
C /12
12
  

 #  
 #  
 
 
   
   

 
 
!   
!   

 + 
+  ! 
 !

  #
# 

 
    
 
 
   .
  .!

 ( 
 ( 
!   
!   

   .
  .
 
 (
( 

  
  
 
352
8R  ^, 
35
 
35
  /

  
 

  ( !
  ( 
8
   
  

$  
$  
  
  8
8  
 1
 $
 $
*(1
*(
/*(
*

      
                 
    !  
     !
    "
#  $    %!  &
 
 
 
 
 
 
 
 
 
     
 
 
 
 
 
 ,   )   9    *) .   .  2             7    9    *)     #   
( !      $
&(/*(1(35235,(7$5<,1)2
   *)  
   *) 
50$7,21
7
$7
0$7
50
50
25
25

      
                 
    !  
     !
 1   "
#  $    %!  &
/:*.%
8-.24*. 79 53426 /55.550.135 97( '/3).135 E)3- 8(7557>.( 71 *.1/*)270)2. /93.(
'(7B(.55)71)1)1>.53)B/37(H58-7)8.(0C2/65I868*. J 707(.3-/1
E..A5/93.(*/532/679*/53868*.793(./30.13)1(0
(78.24(.
>.(6 68*.
/6F2/65
 68*.
/6@C
 68*.5@
/6
>.(6+2/65
93.( 68*.
/6
3(./30.13
)58713)14/3)71
 7**7E4'97(
'/3).135/93.(

 7**7E4'97(
171
3)
3 
4    !# ?   ' ! 
 4 ?' !   
G
G
6 
G
G
 -  .  
G
G
G
G
    
G
G
G
G
 9   3 -1
G
G
- 
   
L 
   
   
G
8(      

G
G
%# 4#"
G
G
G
G
G"
9   
3 
L9   
 
% ,
G
*  : !/ 
G
G
       L  
G
G
G
G
 9L*)   C7 7 (    
!#
G
G2
9 
 
  
  
  
G
*!   
G
  3 ##&
G
G
G
?# ##
G
G
6   .7 (   !7  !7  !$
     ! (        -  .   (       *- 7    (7   7  67 . (    
J-    . 7 (   !    %= 7 (   !     % 7  !  $ 
       ! 7 ( 7  7 ! !  7  7  7   ((7 C ! !7 %9 
 '?97 %9  '97   7 !  7  (     7     $
1 8   !!      2    .         3 -      # ! 
   !  (  %!!  $,   $2 )      A ! 7  #  
&(/*(1(35235,(7$5<,1)250$7,21
'/
'


 7**7E4
 7**7E4
171
1
)
3
)
3 

0$7,
50
2 0
25
)2
)2
G
)2
)2
)2
1)2
)2
G
1
,1
G
< ,
5<
$5
G
$5
$5
$5
(7$
G
G
(7
(7
(7
(7
G
5,(
35
G
23
523


G
52
52
52
52
 
  

35
 
 

( 3
 
 
(1
3 ##
3 ##
*(
##
##
/*
(/
6  
6  
    !
  !
J

      
                 
    !  
     !
    "
#  $    %!  &
     . 3 -         (      (      #   !  
(  %!!  $,   $2$
% !   (   (  ! !   C    +! $
"%# # . (    !       .!$
,9   L9          8  7 17 27  7  .  $
2 9 .  L   *)      &   ^       . ! !   ! .  #   
     # # .  #   ! # $  9 L*)        ( !   
   .!   ! .        !     !$ 
&   3 ##    !         +  !      #7 .#    
$
 . (   .   #      !       # ## # &   ^    
    ,O    ! #         .!  !  !  _         
    !    # !    *L *  ( 7 . #    7  .     . 
(  $
  . (   .   #   9 L*)    # ## # &   ^        
,O    ! #         .!  !  !  _             !  
  # !    *L *  ( 7 . #    7  .     . (  $
& '  %
I         (   !      !  !    
( $          # ( !!       (     
(  7   !(        (       .  ( $
D, -./0.120.134'2/3.2/:*.@793-.'(73787*
.*.3)7179  /::(.>)/3)71
22)3)7179 /::(.>)/3)7197( 7**)84*/(60'-70/
C, -./0.120.134'2/3.25.83)71,,793-.'(73787*
   %
3  7  !         !            
       ! .       $  ) .  !   ! 
.   #       9   *   7  2$  J    .  
   #   7  .             ! . C     
7     (   !U 9       . A   !    $ ) . 
  !     ! 9       !     .   (   81   82 
9       !    3 !   !          *   7 
 2$ 9  .  (       9   .    9  
.  .     12  .   3 7 (   .    - $  ) 
  . 3 7 !#   9   . !!      3%7 
C7 )C7 *( ,%   %    !  (A 9  %   $ ) .  
        !  . !  ! (       .  
          $ 9    (  3 -       9  . 
     `    1 . A           3 !      
 ! !  !    % !#    !   +   $ 
&(/*(1(35235,(7$5<,1)250$7,21


 

 .
 .


  
  

    ! 
    ! 
  $
 $
  !
  !
  
 

$
$
-70/
-70/
, 793-.'(
793-.'

 

 
 . 
. 

 
    
   

7  . 
 . 
   !
   !

  !
 !
 
  
 
 
 .
.
 .  
 .  

 .
. 3
C7
C7 )C7 
)C7 *(
*(
  
  
  
  

      
                 
    !  
     !
 "   "
#  $    %!  &
% 7  . (     !  +!     # #   
   ! 7        !     ' #  7  2$ 
3  7         C   /   ! /      
      7 !     (     8 +!     ( ! (   
 /     8 !    ! /    !    ($        
   !∀9 7    C     ! /  .     $ 
      (    !a9     !    #    !a9  
     $ 
9 (    (#              7    +!    
!     !!    !  !  # #         ( 9 7  
.                !     ! #     
  7 #    (     !!  (     !   $
& %
@!   . ! $
+, -./0.120.134'2/3.25.83)71,,793-.'(73787*
  %
             . !       7    ! 
! !  #  # $  )  7          7   7  ( 
!    # #      !   .      !     (  . 
+ (  8 I7  N ; 7  1$  )        =:       
   !      !$ $             2   ! . ! 
# =:7    1& !     JC7  ,$      !       ! 
!    *7    ! !       *  " ! !   *   ! 
.    9 7  ,$  3     ! .  !     !7  .    # ! 
.  # !  ( /  ( ! $  )  7           1 # # . 
 !  O    (  !  O$   )               ! 
     !$ $      8       2   ! . !     =:
   =:7        2& !      // 7  2$     !     
 (I# !     "O   ! .  $ )   ! ))    =:   
=:7           L1 %4 .  !   O    (  !  O 
 :( 7  2$ -    !   (# 7     (     
#           ! .     !  $
    %
9 !          # (    ! . 
!L  =:    =:    =:    =:   =:  
# =:$  9  L      .     !$ $          8 >
8    2  7      .C  =:   =:      !    =:$  
 .     !   .   =:   =:$  
)  .  !       #       7 8- 7 
    3  7   # !    ?** . O  =:   "O  =:
7 !#  JC7  2$ ) =: 7    1& !    .        
 
    
 
9 7  
7  
   
   

 !   
 !   
 
  
 
   
   
  
 
  
   
   
 
    
  

JC7 
JC7  
 
  
    *
  

 .
$ 

)
) 


 !  O
 !  O
  
 
    
  
   2& !
 2& !
  "O
"O  
     
    
$$ - 
-  
  
  
 %
 %
/*
!
!
 
!L
!L

#
# =
8    
8  


      
                 
    !  
     !
 ,   "
#  $    %!  &
   $        1 !    (      )    !  ?** 
  O .   $ 9 !   O    *       *7   !  O   
*$ 9       !  . $,       3 . $"   $ 9    
      1 # # .   (  !  O             # 
# .  !  1O7  !   ,O7    (  !   O$  :( 7  &$ ) 
     =: . .   = # (  "7     2 !    
 $  %    7  27 &   ! . #(   !     P/7  2$  
9    . ""  >2  $  9                    
. $1  $1>& $  9 !  #        >2 !   7   O  &L&
  !  # !  ( /  (  $  9 ?**      . 1O  "L&7 
 O  L&   ! !    *L    *7   2O  L& ! ! $  9 
  "O !  ( $  9             1 # # .  !  O 
   (  !   O7    O7   O  (  !  O  P/7 
 2$
&   %
@!   .  #(
, -./0.120.134'2/3.25.83)71,,793-.'(73787*
    %
& .    =  %    .    4 !7 )7  %$ 
)   ! .   /   #     +     !(  ! 
+     # !     !  $           !(     
. #          2 $ 8+   1  L .      17 
& 7  ,      2      1       1     2  
$  
& %
@!   .  #($
, -./0.120.134'2/3.25.83)71,,@793-.'(73787*
  %
    ( #  ! . 8      $  *      
          #     ! .  .    
C 8  .   8 .       A   (  $  *    
   8 7  8 .       A   (  7 
 .   !  ", O    !$          .  (   
  *-    ! .          " *-    
!      .      . #   "   !  
   !  . 11 .C$     !  . #  !! +  , O   ! 
.   !   !          O      ! $  ' L1 
 !    (  !           %4   .       7 
(   ( .     L  !   7  "$
&(/*(1(35235,(7$5<,1)250$7,21
 
 
&L&
&L&
 "L&7
 "L&7
 $  9
 $  9
 !  
 !  
 O
 O  P
P
. 
.  
 
  
  
  $  
 $ 
+  
+  
 
 1 

'2/3.25.83)
2/3.25.83
 ( #
 ( 
  
  
8 
 .
.
 
8

 . 
 . 

  *- 
*- 
 
 

      
                 
    !  
     !
 2   "
#  $    %!  &
    %
    ( #  ! . 8   !           
! .  !       .  ) C   ! 
     .    A   (   .   .      
(  $  ) 87    .     L           8
 L  8   !  $ *       8 7  8 
.       A   (  7  .   !  ", O   
 !$          .  (     *-    ! . 
         " *-    !      .    
  . #   "   !     !  . 11 .C$  
   !  . #  !! +  , O   !$ ' L1  !  
  (  !           %4   .       7 (   ( 
.     L  !   7  "$
& %
@!   .  #($
, -./0.120.13/22.2/1.E5.83)71,,
,,  *)1)8/*342).579.1/*)270)2.)1 -(71)860'-7863)8.4A.0)/
      !  ( #  .  #     ))9  ! . 
!L      ;7  "   ;7  ,7  3I 7  2$  )    
! . !L    .  .        +    A  2    
;7  "   ;7  ,$  *       .   # !     O . 
2O   ! #   *  "O #  *$  9   3    &$1     $  >
20   $  3  2O       .    !   L    2O . 
              %4 ! $ ?  !  %4 !  .     
    ON '   1   (  !  1O7  '   1  !  ,O$  
    (   . !   .  !  O$  )    ))9   3I 7  27 
          . #  ! . !L   $  
   .       2     2    !  $  %  # 
!      O .  (# .   *  ,O7    *   O7  *   O$   !!  
.           +  (#7 1O # '   !  "O '  
  (  !$
, -./0.120.134'2/3.25.83)71,793-.'(73787*
   %
9         . (  2 $ 9               
     7     . (  &  $
9  2     (          !     
  !  L     $
& %
&(/*(1(35235,(7$5<,1)250$7,21
. 
. 
 
 
1 .C$ 
.C$ 
 !
 ! 

  
  
7863)8.4A
63)8.4
#  
#  
;7
;  
 
. 
  
 
    
    
#
#  
 *
   
   
4 
4 
! 
! 

  (  
  ( 
   . 
. 
  
   .
 
 

  (# 
  (# 
   
   
 ++
$$
/0.120.1
/0.120.1
 
 
(/
9
9  
 
  
  

      
                 
    !  
     !
 &   "
#  $    %!  &
          2        !  L     $
@, -./0.120.134'2/3.29773173.5793/:*.173.2)1,,793-.'(73787*
  
*    !! #            7 ! # (  7    
# U   !     ! !(        7 .7 
! 7   7  #      .   !     
      7 . !!($
*+ (       ( ! # "   8 "  #         # " 
 $ 
   
*    !! #            7 ! # (   7( (.9.(.18.
*)1A5'(7>)2.2/:7>.)15.83)71,,    # U   !     ! !( 
       7 .7 ! 7   7  #    
  .   !           7 . !!($
*+ (       ( ! # "   8 "  #         # " 
 $  7( 3-. '(.>.13)71 79 8637A)1. (.*./5. 5612(70. /5578)/3.2 E)3- 3-. 3(./30.13 79
)34;)0/: K0B790.3-6*'(.21)57*71.7(.L4)>/*.13/(./88.'3.271 
&   
9   !        !   ! # *+ ($
, -./0.120.134'2/3.23/:*.?173.2)15.83)71,,793-.'(73787*
   %
    
7;)8)36(/2.
83)71.L4)(.2
=.  # ! W '  !! 
 ! 3-)5/''*).571*6373-75.
37;)8)3).5 E-)8- :.B)1 7( E7(5.1
E-)*.7153426 

:   !  

J   +  #   Z '     + 
 .   #
&(/*(1(35235,(7$5<,1)250$7,21
7


  
  #
#  "

  
  7
   
  

  

!
 
 7  #
 7  #
 !!(
 !!(
" 
"  # 
 #
0.
0. /5578)/
/5578)/
(./88.'3.2
./88.'3
! 
 
2 )15.83)71
)15.83)

52
52
52
52
  !!
  !!
*).5
.5 71*6
71*6 37
37
:.B)1
:.B)1
7(
7(
3
*(

      
                 
    !  
     !
   "
#  $    %!  &
 % 9  %9 _  + 
@=
4+    7  
 !     
#  
=L%
%9 _   Z + @=  9  
(( Z $ + @=
    N   
+  # 
=L%
%9 _   Z  + @=   9  
(( _ $ + @=
:      N 
 .C  %9 
   ((    
(
*  
 
  
  
  
     #     
#  Z 1 $  )  #  
!   (  1 7  
        ( 
 (     #7  
.C    #   
      $  ) 
 #        
( .  2 7  
  
    
  
( 
 $
%9 _  + @=   9  (( _ 
$ + @=
:      N 
 .C  %9 
   ((    
(
*  
 
  
  
  
     #     
#  Z 1 $  )  #  
!   (  1 7  
        ( 
 (     #7  
.C    #   
      $  ) 
 #        
( .  2 7  
  
    
  
( 
 $
      *
)  ! +!  %4  A    ! 7  !    (     
     %4   #    !(  (  ( "$ ?  %4  
 #7  !     (C           # A  9( "7   
  ( ,  2               $ 8   .  7 (   
 +       7 .   ( $ 
)         %4  !      .  +     , 
 !       A     ( . # (  $
9          .       (        
 ( C (       . (         8    .   
         .    $
& %
9         I          #  +$
9        I L!          7     %4$
&(/*(1(35235,(7$5<,1)250$7,21
  
  
7 

  
  (
(
#7
#7 

# 
#  
 
  
  
 
 
  
  
. 
.
 2
 2
   
   
$

$7
  
* 
 

  
  
# 
# 
! 
!

1
23
5<
 A
A
 # 
 #
 
  
  (
  
  

  7 .
  7 .
 
 

  
  

  
 
( 
( C
C
 
 
 
 
&

      
                 
    !  
     !
   "
#  $    %!  &
?, -./0.120.134'2/3.25.83)71,,D793-.'(73787*
   %
' .    $$ ' 37 ' 37  ! 7 !  .   $      ( 
  ! !7 (   ( !( (  #        # 
    #7        ( !! !$ 9   (     .  
%        ?  U  % ?  4 !      ?    4? 
7              *3 !$
& %
)        #7   !     .    /  .  $
D, -./0.120.134'2/3.25.83)71,,C793-.'(73787*
  %
8  (     !      .         2  !  
+!           M
    %
8  (     !      .         2  !  
+!            /1297(3-.'(.>.13)71798637A)1.(.*./5.5612(70./5578)/3.2
E)3-3-.3(./30.1379)34;)0/:71 M
&   %
9   !        !   ! # *+ ($
C, -./0.120.134'2/3.25.83)71,793-.'(73787*
  %
71./((7E5')(/3./12)7'56
-    . !   ( !     A    !   . 
      *$ 9 (    . !    ( !    2       
 * #  . (  $
    %
71./((7E)7'56
@ (    . ( !     A    !   .   
    *$ 9 (    . !    ( !    2        * # 
 . (  $
&   %
-    . !  (      *        ( !7 (  ! . (   
  #$
&(/*(1(35235,(7$5<,1)250$7,21
  

2
2 

   
   
 
1798637A)1
1798637A)1
  ! 
 ! 
,
,793-.'
793-
)7'56
)7'56

 

   *$ 9 (
 *$ 9 (
(  $
(  
 %
 %
*(
/(
/((7E)7'
E )7

 ( 
( 
 
   
  
 .
.

      
                 
    !  
     !
    "
#  $    %!  &
 
 
 
 
 
 
 
 
 
 
 
 
 
&(/*(1(35235,(7$5<,1)250$7,21
1)2
7$
,(7
5,(
35,
235
23
352
35
( 3
1(
(1(
*(1
*(
/*
(/*
&(

      
                 
    !  
     !
   "
#  $    %!  &
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
&(/*(1(35235,(7$5<,1)250$7,21
25
< ,1
< ,1
5<
(7
5,(7
35,(
352
35
( 3
1(
(1(
(1
*(
/*
(/*
&(/
(/

      
                 
    !  
     !
1   "
#  $    %!  &
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
/*(1(35235,(7$5<,1)250$7,21
7
$7
50$
50
25
)2
1)2
< ,1
5<,
(7$
35
52
352
35
( 3
1(
(1(
/*(
(/*
&(/
&(
&

      
                 
    !  
     !
   "
#  $    %!  &
@, -. /0.120.13 4'2/3.2 5.83)71 ,, 79 3-. '(73787* J M4/*)36 79 )9. 3)0. '7)135 < /3/
87**.83)71/123)0)1B
  %
<    . (      !      9(   

 L(  . ,  !      / 7 

      8

  1   87

             
% ^ ,    . . . (  .$
    %
<    (    (  !  , !!   !    ( .  9( . 
 !        #$ 9 . (    (       
!L# 7            !     $
 . ( C     !  A     !    ! ($ 9 # 
      !  A       $ 9         !  
A  . (   
<    . (   ,   !      9(   

 L(  . ,  !      / 7 

      8

  1   87

  "   ,87

  2   &87

             
% ^ ,    . . . (  .$
&   %
9   .      <   $
, -./0.120.134'2/3.25.83)71793-.'(73787*
  
:(  97 )/  7  $         ! !    !    
! . !         !  $$    7 1,"7 B  $  &$
    
&(/*(1(35235,(7$5<,1)250$7,21
   (
   (
  
 ( 
 ! 
 ! 
  
  

$ 
$ 9
9
  
  9(
9(  
 !    
 !    
7
&87
87
   
   
 . . (
 . . (
 %
 %
*(
 
 
, -.
-./0.
/0.
 
 
&

      
                 
    !  
     !
"   "
#  $    %!  &
:(  97    )7 B '7 6  B7 JC :7 - ;7 J ;7 4#: %7
9C ;7    87 P B-7 9  B$         ! !    
!    ! . !         !  $- B :  $ 3(  &7
 4!(    !$
    
9  B7    )7 B '7  $     ?   !    O *!  * 
  . *!L*    = : C  !  $        %: % 
 %(7 = #  ,N   "
JC :7    )7 9  B7  $     *!   *!L*  %# 
= : C   !       9   -  9     *+ ( 9 $     
  = #  ,N  "
   
P/ 7 J/ 947 6  B7  $  4        ?  !  ! 
. *!   *      !   *       $       %: 
%  %(N = #$  2N    " $
&   
 !
?, -./0.120.134'2/3./''.12);,97(/55.550.1379'(7B(.55)>.2)5./5.
  
(7B(.55)>.2)5./5. )1'/3).1357(171(.5'712.(5
b %!!    .  7 . '8 _      7         !
    
b %!!    .  7 . N00   7         !
&   
9      .    (     (       .  $
&(/*(1(35235,(7$5<,1)250$7,21


#
#
$    
     
 
  !
 !
 
  

0.1379'(7B
.1379'(
1(.5'712.(
1(.5'712.(
     
    
 7 .
7 . 

   . 
   .