Conditions: Lymphoma, Non-Hodgkin
Keywords: CC-122 Phase1 solid tumor non-Hodgkin's lymphom
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 15
Healthy volunteers: no

Brief summary:
To determine the safety and tolerability of CC-122 when administered orally to adult Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL) and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Detailed description:
This is a phase 1, multicenter, open-label, dose-escalation study that will evaluate the safety, tolerability, (Pharmacokinetics) PK, and preliminary efficacy of CC-122 in Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL).

Subjects will receive ascending dose levels of CC-122 from Cycle 1 onwards to measure PK and to determine safety and tolerability.

An initial cohort of at least three subjects will be given CC-122 at a dose of 2.0 mg on an intermittent dosing schedule (5 continuous days out of 7 days per week) and 3-6 subjects will be enrolled in subsequent dose levels. Dose escalation for subsequent cohorts will proceed according to a standard dose escalation design (3+3 design) (Storer, 1989) to establish initial toxicity.

Arms:
arm 1: CC-122 is administered orally, on a 5 continuous days out of 7 days per week intermittent dosing schedule.

Interventions: intervention 1: CC-122
Intervention descriptions: intervention 1: 5 continuous days out of 7 days per week intermittent dosing

Protocol document:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 1, Multi-center, Open-label Dose-escalation Study to Assess the Safety, Tolerability, and 
Pharmacokinetics of CC-122 Administered Orally to Adult Japanese Subjects With Advanced Solid 
Tumors or Non-Hodgkin's Lymphoma 
 
 
NCT Number: NCT02509039 
Document Date (Date in which document was last revised): December 13, 2016 


EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
1
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
TITLE PAGE
A PHASE 1, MULTI-CENTER, OPEN-LABEL 
DOSE-ESCALATION STUDY TO ASSESS THE SAFETY, 
TOLERABILITY, AND PHARMACOKINETICS OF 
CC-122 ADMINISTERED ORALLY TO ADULT 
JAPANESE SUBJECTS WITH ADVANCED SOLID 
TUMORS OR NON-HODGKIN’S LYMPHOMA
INVESTIGATIONAL PRODUCT (IP):
CC-122
PROTOCOL NUMBER:
CC-122-ST-002
ORIGINAL DATE FINAL:
06 Feb 2015
AMENDMENT No. 01 DATE FINAL:
09 Apr 2015
AMENDMENT No. 02 DATE FINAL:
28 Mar 2016
AMENDMENT No. 03 DATE FINAL:
13 Dec 2016
EudraCT NUMBER:
Not applicable
IND NUMBER:
Not applicable
SPONSOR NAME/ADDRESS:
Celgene K.K.
JP Tower 10F, 2-7-2 Marunouchi
Chiyoda-ku, Tokyo 100-7010 Japan
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.
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MEDICAL MONITOR/EMERGENCY CONTACT INFORMATION 
Contact Information: Celgene K.K. medical monitor
Name:
Title:
Address: JP Tower 10F, 2-7-2 Marunouchi Chiyoda-ku Tokyo, 100-7010 Japan
Phone:
E-mail:
Contact Information: Clinical research physician
Name:
Title:
Address: 1500 Owens Street, Suite 600, San Francisco, CA 94158
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center: 
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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Protocol CC-122-ST-002
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name: _______________________________________
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, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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Protocol CC-122-ST-002
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PROTOCOL SUMMARY
Study Title
A phase 1, multi-center, open-label dose-escalation study to assess the safety, tolerability, and 
pharmacokinetics of CC-122 administered orally to adult Japanese subjects with advanced solid 
tumors or non-Hodgkin’s lymphoma
Indication
Advanced solid tumors or non-Hodgkin’s lymphoma (NHL)
Objectives
The primary objectives of the study are:

To determine the safety and tolerability of CC-122 when administered orally to adult
Japanese subjects with advanced solid tumors or NHL and to define the maximum
tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

To determine the plasma pharmacokinetics (PK) of CC-122 in Japanese subjects with
advanced solid tumors or NHL
The secondary objective of the study is:

To make a preliminary assessment of the antitumor activity of CC-122
The exploratory objectives of the study are:

To evaluate the plasma PK of CC-122 formulated capsules and compare results to the
plasma PK of CC-122 active ingredient in capsule (AIC)

To assess the tolerability of CC-122 formulated capsules

Study Design
This is a phase 1, multicenter, open-label, dose-escalation study that will evaluate the safety, 
tolerability, PK, and preliminary efficacy of CC-122 in Japanese subjects with advanced solid 
tumors or NHL.
Subjects will receive ascending dose levels of CC-122 from Cycle 1 onwards to measure PK and 
to determine safety and tolerability.
An initial cohort of at least three subjects will be given CC-122 at a dose of 2.0 mg on an 
intermittent dosing schedule (5 continuous days out of 7 days per week) using the active 
ingredient in capsule (AIC) and 3-6 subjects will be enrolled in subsequent dose levels. Dose 
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escalation for subsequent cohorts will proceed according to a standard dose escalation design 
(3+3 design) (Storer, 1989) to establish initial toxicity.
The first dose level will be assessed in subjects with solid tumors or NHL, and subsequent dose 
levels will only be assessed in subjects with NHL.
All subjects will be treated and observed for at least 28 days (Cycle 1) after the first dose of 
CC-122 (dose-limiting toxicity [DLT] evaluation period) before the dose level is escalated in 
another cohort. The provisional dose levels to be evaluated are shown in Table 1.
A standard escalation schedule will be initiated in order to establish the MTD by assessing the 
occurrence of DLTs. Smaller increments and additional subjects within a dose cohort may also 
be evaluated as necessary to determine the MTD and RP2D more precisely.
A dose level will be considered tolerable if 0 of 3 treated subjects experiences a DLT during the 
DLT evaluation period for each respective group. If 1 of 3 subjects experiences a DLT, 3 
additional subjects will be enrolled and treated at that dose level. A dose will be considered a 
non-tolerated dose (NTD) when two or more out of six evaluable subjects in a cohort experience 
DLTs during the DLT evaluation period. The MTD is defined as the last dose level below the 
NTD with zero or one out of six evaluable subjects experiencing DLTs during the DLT 
evaluation period. At least 6 subjects will be enrolled at the MTD/RP2D.
The decision to either evaluate a higher dose level or declare the MTD or RP2D will be 
determined by the Safety Review Committee (SRC), which includes the principal investigator 
and Celgene’s medical monitor (see Section 8.2.1), each time all clinical and laboratory safety 
data for a given cohort are available for review.
The SRC may decide to identify an RP2D based on safety, PK, and preliminary efficacy 
information, which will not exceed the MTD from global CC-122 trials in various indications.
Study Population
Japanese men and women, 20 years or older, with advanced solid tumors, or NHL, including 
subjects who have progressed on (or were not able to tolerate) standard therapy or for whom no 
standard anticancer therapy exists.
Approximately 15 subjects will be enrolled and treated; however, the total number of subjects 
enrolled will depend on the number of dose cohorts needed to establish the MTD.
Length of Study
This study will consist of 3 periods: screening, treatment, and end of treatment & follow-up.
During the screening period, lasting up to 28 days, subjects will undergo assessments to 
determine their eligibility. Subjects who qualify for enrollment into the study will enter the 
treatment period. Each subject will be administered oral doses of CC-122 in the treatment period, 
which starts on Cycle 1 Day 1 where investigational product (IP) is administered on a 5 
continuous days out of 7 days per week intermittent dosing schedule (Cycle = 28 days).
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If subjects continue therapy with CC-122, subsequent cycles are 28 days long on a 5 continuous 
days out of 7 days per week intermittent dosing schedule.
Subjects may continue CC-122 without interruption for as long as they derive benefit, as 
assessed by the investigator. Treatment will be discontinued if there is evidence of clinically 
significant disease progression, unacceptable toxicity or if the subject/physician decides to stop
treatment.
The follow-up period will begin at the discontinuation of IP treatment. Subjects will have an end
of treatment (EOT) assessment during a visit within 21 days of the last dose of IP and a follow-
up visit 28 days after the last dose of IP to obtain information regarding new or ongoing adverse 
events (AEs).
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as prespecified in the protocol and/or the 
Statistical Analysis Plan, whichever is the later date.
Study Treatments
The starting dose of CC-122 is a flat dose of 2.0 mg on a 5 continuous days out of 7 days per 
week intermittent dosing schedule using AIC.
The provisional dose-escalation levels are as follows and intermediate or lower doses of CC-122 
may be evaluated as necessary.
Table 1:
Provisional Dose-escalation Levels
Cohort
CC-122 dose
Assessed in subjects with solid tumors or NHL
-1
1.0 mg (5 continuous days out of 7 days per week intermittent dosing) using the 
active ingredient in capsule (AIC) formulation
[only used as necessary if the first dose level is not considered tolerable]
1
2.0 mg (5 continuous days out of 7 days per week intermittent dosing) AIC
Assessed only in subjects with NHL
2
3.0 mg (5 continuous days out of 7 days per week intermittent dosing) AIC
3
4.0 mg (5 continuous days out of 7 days per week intermittent dosing) AIC
4
3.0 mg (5 continuous days out of 7 days per week intermittent dosing) using the 
formulated capsules
After at least 3 subjects have been enrolled in the 4 mg CC-122 AIC cohort (Cohort 3) and this 
dose level is determined to be tolerable, at least 6 subjects will be subsequently enrolled in the 
3 mg CC-122 formulated capsules cohort (Cohort 4) to evaluate for differences in PK and 
tolerability.
Lower doses using CC-122 formulated capsules may be evaluated as necessary.
Intra-subject dose escalation is not permitted unless approved by the SRC.
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Overview of Efficacy Assessments
Subjects will be evaluated for efficacy approximately every 2 cycles for the first 6 cycles and 
every 3 cycles thereafter. The primary efficacy variable is response for all tumor cohorts. Tumor 
response will be based on the Response Evaluation Criteria in Solid Tumors (RECIST, version 
1.1) for solid tumors, and the International Workshop Group (IWG) Revised Criteria for 
Lymphoma (Appendix A, Section 19.1).
Overview of Safety Assessments
The safety variables for this study are adverse events, clinical laboratory assessments, 12-lead 
electrocardiograms (ECGs), left ventricular ejection fraction (LVEF) assessments, physical 
examinations and vital signs.
Overview of Pharmacokinetic Assessments
The PK of CC-122 will be determined from serial blood collections during the first treatment 
cycle.
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................5
1.
INTRODUCTION..................................................................................................16
1.1.
Overview of CC-122...............................................................................................16
1.1.1.
Mechanism of Action .............................................................................................16
1.1.2.
Preclinical Toxicology............................................................................................17
1.1.3.
Human Experience and Safety of CC-122...............................................................18
1.2.
Study Rationale/Purpose.........................................................................................20
2.
STUDY OBJECTIVES...........................................................................................22
2.1.
Primary Objectives .................................................................................................22
2.2.
Secondary Objective...............................................................................................22
2.3.
Exploratory Objectives ...........................................................................................22
3.
STUDY ENDPOINTS............................................................................................23
3.1.
Primary Endpoint(s) ...............................................................................................23
3.2.
Secondary Endpoint(s)............................................................................................23
3.3.
Exploratory Endpoint(s)..........................................................................................23
4.
OVERALL STUDY DESIGN ................................................................................24
4.1.
Study Design ..........................................................................................................24
4.1.1.
Evaluation of Dose-limiting Toxicities....................................................................25
4.2.
Study Design Rationale ..........................................................................................25
4.3.
Study Duration .......................................................................................................26
4.4.
End of Trial ............................................................................................................26
5.
TABLE OF EVENTS.............................................................................................27
6.
PROCEDURES......................................................................................................31
6.1.
Screening Assessments...........................................................................................31
6.1.1.
Informed Consent ...................................................................................................31
6.1.2.
Patient Demographics/Medical History/Diagnosis and Extent of 
Cancer/Prior Therapies ...........................................................................................31
6.1.3.
Assessment of Inclusion/Exclusion Criteria ............................................................31
6.1.4.
Concomitant Medications and Procedures...............................................................31
6.1.5.
Information to be Collected on Screen Failures and Non-treated Subjects...............31
6.2.
Safety Assessments.................................................................................................32
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6.2.1.
Physical Examination, Height and Weight, Assessment of Hydration Status...........32
6.2.2.
Vital Signs..............................................................................................................32
6.2.3.
Eastern Cooperative Oncology Group Performance Status......................................32
6.2.4.
Pregnancy Test .......................................................................................................33
6.2.5.
Contraceptive Counseling.......................................................................................33
6.2.6.
Clinical Laboratory Tests........................................................................................34
6.2.7.
Cardiac Imaging .....................................................................................................35
6.2.7.1.
12-lead Electrocardiograms ....................................................................................35
6.2.7.2.
Left Ventricular Ejection Fraction...........................................................................35
6.2.8.
Ophthalmologic Examination .................................................................................35
6.3.
Efficacy Assessments .............................................................................................36
6.4.
Pharmacokinetic Assessments.................................................................................37
38
7.
STUDY POPULATION.........................................................................................39
7.1.
Number of Subjects and Sites .................................................................................39
7.2.
Inclusion Criteria....................................................................................................39
7.3.
Exclusion Criteria...................................................................................................40
8.
DESCRIPTION OF STUDY TREATMENTS........................................................42
8.1.
Description of Investigational Product(s)................................................................42
8.2.
Treatment Administration and Schedule .................................................................42
8.2.1.
Safety Review Committee ......................................................................................42
8.2.2.
Definition of a Treatment Cycle..............................................................................43
8.2.3.
Starting Dose Level and Provisional Dose Levels ...................................................43
8.2.4.
Definition of Evaluable Subjects.............................................................................43
8.2.5.
Definition of Maximum Tolerated Dose and Non-tolerated Dose............................43
8.2.6.
Definition of Dose-limiting Toxicities ....................................................................43
8.2.7.
Criteria for Dose Escalation in the Next Cohort of Subjects....................................44
8.2.8.
Definition of Stopping Criteria for Dose Escalation ................................................45
8.2.9.
Permitted Dosing Adjustments................................................................................45
8.2.9.1.
Criteria for Dose Reduction ....................................................................................45
8.2.9.2.
Intra-subject Escalation...........................................................................................46
8.2.9.3.
Treatment Delay.....................................................................................................46
8.2.9.4.
Dose Modification and Management of Toxicities..................................................46
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8.2.9.5.
Overdose ................................................................................................................50
8.3.
Method of Treatment Assignment...........................................................................51
8.4.
Packaging and Labeling..........................................................................................51
8.5.
Investigational Product Accountability and Disposal ..............................................51
8.6.
Investigational Product Compliance........................................................................52
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................53
9.1.
Permitted Concomitant Medications and Procedures...............................................53
9.2.
Prohibited Concomitant Medications and Procedures..............................................54
9.3.
Required Concomitant Medications and Procedures................................................54
10.
STATISTICAL ANALYSES..................................................................................55
10.1.
Overview................................................................................................................55
10.2.
Study Population Definitions ..................................................................................55
10.3.
Sample Size and Power Considerations...................................................................55
10.4.
Background and Demographic Characteristics........................................................55
10.5.
Subject Disposition.................................................................................................55
10.6.
Efficacy Analysis....................................................................................................56
10.7.
Safety Analysis.......................................................................................................56
10.8.
Interim Analysis .....................................................................................................57
10.9.
Assessment of Pharmacokinetics ............................................................................57
57
11.
ADVERSE EVENTS..............................................................................................59
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................59
11.2.
Evaluation of Adverse Events.................................................................................59
11.2.1.
Seriousness.............................................................................................................59
11.2.2.
Severity/Intensity....................................................................................................61
11.2.3.
Causality ................................................................................................................61
11.2.4.
Duration .................................................................................................................62
11.2.5.
Action Taken..........................................................................................................62
11.2.6.
Outcome.................................................................................................................62
11.3.
Abnormal Laboratory Values..................................................................................62
11.4.
Pregnancy...............................................................................................................62
11.4.1.
Females of Childbearing Potential ..........................................................................62
11.4.2.
Male Subjects.........................................................................................................63
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11.5.
Reporting of Serious Adverse Events......................................................................63
11.5.1.
Safety Queries ........................................................................................................64
11.6.
Expedited Reporting of Adverse Events..................................................................64
12.
DISCONTINUATIONS .........................................................................................65
13.
EMERGENCY PROCEDURES.............................................................................66
13.1.
Emergency Contact.................................................................................................66
13.2.
Emergency Identification of Investigational Products .............................................66
14.
REGULATORY CONSIDERATIONS...................................................................67
14.1.
Good Clinical Practice............................................................................................67
14.2.
Investigator Responsibilities ...................................................................................67
14.3.
Subject Information and Informed Consent.............................................................67
14.4.
Confidentiality........................................................................................................68
14.5.
Protocol Amendments.............................................................................................68
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................68
14.7.
Ongoing Information for Institutional Review Board/Ethics Committee .................69
14.8.
Closure of the Study ...............................................................................................69
14.9.
Compensation for Injured Subjects .........................................................................69
15.
DATA HANDLING AND RECORDKEEPING.....................................................70
15.1.
Data/Documents .....................................................................................................70
15.2.
Data Management...................................................................................................70
15.3.
Record Retention....................................................................................................70
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................72
16.1.
Study Monitoring and Source Data Verification......................................................72
16.2.
Audits and Inspections............................................................................................72
17.
PUBLICATIONS ...................................................................................................73
18.
REFERENCES.......................................................................................................74
19.
APPENDICES........................................................................................................75
19.1.
Appendix A............................................................................................................75
19.1.1.
Guidelines for Tumor Response Evaluation ............................................................75
19.1.1.1.
Solid Tumors..........................................................................................................75
19.1.1.2.
Lymphoma .............................................................................................................75
19.2.
Appendix B ............................................................................................................76
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19.2.1.
CC-122 Pregnancy Prevention Risk Management Plan ...........................................76
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LIST OF TABLES
Table 1:
Provisional Dose-escalation Levels...........................................................................7
Table 2:
Provisional Dose-escalation Levels.........................................................................24
Table 3:
Table of Events.......................................................................................................27
Table 4:
ECOG Performance Status Scale ............................................................................32
Table 5:
Clinical Laboratory Test Parameters .......................................................................34
Table 6:
Tumor Assessments................................................................................................36
Table 7:
PK Sampling Time Points.......................................................................................37
Table 8:
DLT Criteria...........................................................................................................44
Table 9:
Example of Dose Reduction Steps ..........................................................................46
Table 10:
Guidelines for Dose Modifications of CC-122 Related Toxicities ...........................47
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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................24
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1.
INTRODUCTION
1.1.
Overview of CC-122
CC-122 is a pleiotropic pathway modifier (PPM), a novel class of compounds with multiple
activities, which include immune modulation of several immune cell subsets including activation 
of T cells and natural killer (NK) cells; antiproliferative activity in multiple tumor types and 
antiangiogenic activity as demonstrated by inhibition of endothelial cell sprout formation and 
growth factor induced endothelial cell migration.
CC-122 is a nonphthalimide analog of thalidomide that retains binding affinity to a protein called
cereblon (CRBN), a member of the Cullin 4-ring ligase complex.
1.1.1.
Mechanism of Action
In lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) and whole 
blood, CC-122 inhibits tumor necrosis factor (TNF) release at nanomolar concentrations. In 
addition, CC-122 inhibits the release of other pro-inflammatory cytokines from LPS-stimulated 
PBMCs (granulocyte macrophage colony-stimulating factor [GM-CSF], interleukin-1β [IL-1β], 
macrophage inflammatory protein 1α [MIP1α], MIP1β, IL-6, IL-8, and macrophage-derived 
chemokine [MDC]) while enhancing IL-10 production. The immune modulation is further 
mediated by cereblon-dependent ubiquitination and subsequent degradation of aiolos and ikaros 
in T cells, resulting in the consequent expression of IL-2.  The T cell costimulation of T cells by 
CC-122 also results in expression of IL-3, IL-5, IL-10, IL-13, IL-17A, interferon gamma (IFNγ), 
Rantes, TNFα and GM-CSF. CC-122 is also able to induce relocalization of F-actin to the 
membrane of PBMCs, resulting in a capping structure.
CC-122 enhances immunoglobulin G (IgG)/IL-2 stimulated NK cell production of IFNγ. This 
immunological modulation results in antitumor activity. For example, CC-122 enhances 
NK-mediated antibody-dependent cellular cytotoxicity (ADCC) with rituximab up to 30% 
compared with rituximab treatment alone in follicular (DoHH2), and diffuse large B cell 
lymphoma (DLBCL) (WSU-DLCL2, Farage, RIVA), and Burkitt’s Lymphoma (Raji) cell lines. 
The ADCC-enhancing activity of CC-122 is concentration-dependent up to 0.1 μM. Taken 
together, these data suggest multiple immune modulating activities by CC-122, which have 
potential downstream antitumor effects.
The antiproliferative and cytotoxic effects of CC-122 have been shown in vitro in 11 cancer cell 
lines (Riva, U2932, TMD8, OCI-Ly10, WSU-DLCL2, SUDHL4, K1106P, Farage, Rec-1, 
DoHH2 and H929) and in vivo in four xenograft models (DoHH2, WSU-DLCL2, H929 and 
U87). The in vitro assays used five-day 3H-thymidine incorporation and three-day adenosine 
triphosphate (ATP) production to measure effects on proliferation and cell toxicity, respectively. 
While CC-122 has antiproliferative effects against tumor cells, it has no activity up to 10 μM 
against normal primary human lung fibroblasts and aortic smooth muscle cells.
CC-122 also demonstrated potent antiangiogenic activity in several assays, including a human 
umbilical artery assay, human umbilical vein endothelial cell (HUVEC) proliferation, and a
matrigel plug assay at low nanomolar concentrations. The data demonstrated that CC-122 was a 
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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
17
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
potent inhibitor of endothelial cell sprout formation, a measure of angiogenesis, and is 
comparable in potency to antiangiogenic agents AZD2171 and sunitinib.
CC-122 is inactive against a panel of 266 kinases.
1.1.2.
Preclinical Toxicology
CC-122 has been evaluated in a core battery of repeat-dose (up to 28 days in rats, and 90 days in 
cynomolgus monkeys) and genetic toxicology studies.
In rats, the primary target organs of toxicity after 28 days of repeated administration were the 
kidney, lower urinary tract, and stomach. Secondary to the uremia, systemic effects consisting of 
vascular inflammation were present in multiple organs including the heart. Heart changes were 
only observed at the high dose (300 mg/kg/day); no changes were observed at the next highest 
dose (100 mg/kg/day) (82- to 133-fold and 38- to 59-fold safety margins based on Day 15 
maximum observed concentration [Cmax] and area under the concentration-time curve [AUC]
values for the 3.0 mg dose in humans, respectively).
In a 3-month rat study, daily oral administration of CC-122 resulted in a new histologic finding 
of seminiferous tubule degeneration. Daily administration of CC-122 was well tolerated at all 
dose levels. After the 3 months of dosing, the animals underwent scheduled necropsies. Upon 
microscopic examination, mild to moderate seminiferous tubule degeneration was noted in 100 
and 300 mg base/kg/day dose group animals. Toxicity was not observed in the reproductive 
organs of animals treated at the lower dose of 10 mg base/kg/day. All doses tested were at higher 
exposures than observed with human doses (the exposure at 10, 100 and 300 mg base/kg in rats 
is calculated to be 12x, 43x and 106x the observed human 3 mg dose exposure, respectively). 
Testicular lesions were not observed in a 28-day rat study (67x multiple to human exposure) or 
in 28-day and 3-month monkey studies (up to 53x multiple to human exposure). There were no 
histologic lesions in reproductive organs of female animals in these studies. The significance of 
this pre-clinical finding and the potential and relative clinical risk is unknown at this time.
In monkeys, the primary target organs of toxicity were lymphoid tissues and the lower 
gastrointestinal tract, resulting in systemic inflammation and early euthanasia. In the 28-day 
cynomolgus monkey study, minimal to moderate renal cortical inflammation was also present 
with variable severity across all dose groups (no blood urea nitrogen [BUN] or creatinine 
elevations were present). Renal cortical changes were not different from control animals in the 
90-day cynomolgus monkey study. In the 90-day cynomolgus monkey study, 2 moribund and 1 
terminal sacrifice animal administered 1.5 mg base/kg/day had minimal to moderate iris vascular 
changes (endothelial cell reactivity, and/or edema). Based upon the extent and overall severity of 
the inflammation present in these animals, the vascular changes in the eye were considered to be 
an extension of the systemic inflammatory process. Cardiovascular assessments demonstrated no 
test article-related cardiovascular, electrocardiogram (ECG) or vital sign changes up to the 
highest dose of 6.0 mg base/kg/day in males and females.
Minimal inhibition (9.6%) of human Ether-a-go-go-Related Gene (hERG) potassium ion channel 
was observed at 10 μM (approximately 35-fold safety margin based on Day 15 Cmax values for 
the 3.0 mg dose in humans).
CC-122 was negative in a bacterial reverse mutation assay and negative in the in vitro 
chromosomal aberration assay in human peripheral blood lymphocytes.
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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
18
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
There have been no reproductive and developmental toxicity studies conducted with CC-122 to 
date.  The CC-122 Pregnancy Prevention Risk Management Plan for Celgene Clinical Trials 
(PPRMP) is mandated for all clinical trials.
1.1.3.
Human Experience and Safety of CC-122
Human experience with CC-122 comes from three clinical pharmacology studies in healthy 
volunteers (CC-122-CP-001, CC-122-CP-002, and CC-122-CP-003); from one ongoing first-in-
human phase 1a/1b study, CC-122-ST-001, in subjects with solid tumors and hematologic 
malignancies; one ongoing phase 1b study, CC-122-DLBCL-001, wherein novel combinations of 
CC-122, CC-223, CC-292 and rituximab are administered as doublets or triplets in subjects with 
DLBCL; and three additional studies in specific tumor types in adults, CC-122-HCC-001, CC-
122-NHL-001, and CC-122-CLL-001.
Study CC-122-ST-001 is a study conducted in subjects with solid tumors and hematologic 
malignancies and was designed with two parts: dose escalation (Part A) and dose expansion (Part 
B). Part A was initiated with a starting dose of 0.5 mg administered orally once daily (QD) in 
three-subject cohorts, and increasing in 0.5 mg increments. Part B enrolled 4 parallel tumor 
cohorts, including non-Hodgkin’s lymphoma (NHL), which includes DLBCL and mantle cell 
lymphoma (MCL), multiple myeloma (MM), hepatocellular carcinoma (HCC), and glioblastoma
(GBM). Additional cohorts in DLBCL (DLBCL-2), GBM (GBM-2), primary central nervous 
system lymphoma (PCNSL), and MM (MM-2, with or without dexamethasone) are being 
enrolled. All data are considered preliminary.
Enrollment in Part A of the study has been completed with 34 subjects across seven dose 
cohorts: 0.5 (n=3), 1 (n=4), 1.5 (n=3), 2 (n=3), 2.5 (n=6), 3.0 (n=8) and 3.5 (n=7) mg QD. Dose--
limiting toxicities (DLTs) were observed in two subjects and established the non-tolerated dose 
(NTD) at 3.5 mg QD. DLTs included Grade 3 fever, fatigue and generalized muscle weakness. 
No DLTs were reported for the declared maximum tolerated dose (MTD) of 3 mg QD. Diverse 
tumor types were enrolled, including solid tumors (n=27), lymphoma (n=5) and myeloma (n=2).
As of 13 Jan 2016, in Part A the most common treatment-emergent adverse events (TEAEs) 
(occurring in ≥ 20% of subjects overall) were fatigue, which was experienced by 19 (55.9%) 
subjects; neutropenia, 11 (32.4%) subjects; constipation, 9 (26.5%) subjects; nausea, peripheral 
edema and asthenia, which occurred in 8 (23.5%) subjects each; and dyspnea and vomiting, 7 
(20.6%) subjects each. The system organ class (SOC) categories for which adverse events (AEs) 
were most frequently reported (≥ 50% of all subjects overall experienced an AE that is 
categorized in the respective SOC) were Gastrointestinal Disorders, with 70.6% of subjects 
experiencing an AE in this SOC; General Disorders and Administration Site Conditions, 67.6%; 
Infections and Infestations, 55.9%; and Blood and Lymphatic System Disorders, with 50.0%.
Other than decreases in white cell counts, no laboratory abnormalities showed clear 
treatment-related changes. ECG and left ventricular functioning monitoring were unremarkable. 
Seven subjects had sporadic, asymptomatic, mild troponin-T laboratory test elevations from 
baseline, with no associated cardiac findings, and no clear association with dose or treatment 
duration. The subjects continued on study treatment. Subject monitoring and troponin elevation 
analysis is ongoing.
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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
19
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
Preliminary pharmacokinetic analysis of CC-122 administered to subjects with solid tumors and 
hematologic malignancies demonstrated that CC-122 was rapidly absorbed and eliminated with a 
mean terminal half-life ranging between 8.3 and 25.2 hours. Overall Cmax and AUC increased in 
a linear, approximate dose proportional manner with dose after single and multiple doses. There 
was moderate drug accumulation (about 30% to 40%) following repeated daily dosing. In vitro 
studies indicate mean CC-122 plasma protein binding is approximately 38%.
The preliminary results for best overall tumor response in study CC-122-ST-001 included one 
complete response (CR), in a subject with follicular lymphoma in the 3 mg QD cohort, and two 
partial responses (PR), both in subjects with lymphoma (DLBCL and MCL) in the 3 and 3.5 mg 
cohorts.
Enrollment in the Part B tumor expansion cohorts is ongoing. As of 13 Jan 2016, 171 subjects 
had enrolled, of which 169 were enrolled in the following tumor cohorts in Part B (2 subjects had 
missing tumor type information at the time of the 13 Jan 2016 data cutoff date): GBM (all doses) 
(n=47), HCC (3 mg QD) (n=25), NHL (3 mg QD) (n=25), MM (3 mg QD) (n=27), DLBCL-2 
(all doses) (n=44), and “Other” (n=1).
The most common TEAEs (occurring in ≥ 20% of 169 subjects overall) were neutropenia, which 
was experienced by 87 (51.5%) subjects; asthenia, 69 (40.8%); pyrexia, 51 (30.2%); anemia, 46 
(27.2%); cough and peripheral edema, 38 (22.5% each), diarrhea, 37 (21.9%), and constipation, 
36 (21.3%). The SOC categories for which AEs were most frequently reported (≥ 50% of all 
subjects experienced an AE categorized in the respective SOC) were General Disorders and 
Administration Site Conditions, with 131 (77.5%) subjects experiencing an AE in this SOC; 
Gastrointestinal Disorders, 107 (63.3%); Blood And Lymphatic System Disorders, 97 (57.4%); 
and Respiratory, Thoracic and Mediastinal Disorders (50.3%). Treatment-emergent AEs in the 
Infections and Infestations SOC occurred in 71 (42.0%) subjects.
In Part B dose expansion, there were clear trends toward increased frequency and severity of 
neutropenia in subjects with hematologic tumors, such as MM and NHL, versus subjects with 
solid tumors, such as HCC and GBM.  These data suggest that subjects with hematologic tumors 
with marrow involvement and decreased reserve could be at increased risk for more frequent and 
severe neutropenia. Two intermittent dosing schedules (21 out of 28 days and 5 out of 7 days) 
have been evaluated in order to mitigate neutropenia while achieving similar dose intensity per 
cycle to 3.0 mg QD. The MTD on intermittent dosing in DLBCL subjects was established as 4 
mg for 5 out of 7 days, following 2 DLTs (febrile neutropenia and interstitial pneumonitis) in 2 
out of 5 subjects in the 5 mg 5 continuous days out of 7 days per week dosing schedule. Relative 
to the 3.0 mg QD continuous dose, the 4.0 mg 5 out of 7 day schedule was associated with less 
frequent and less severe neutropenia which required fewer dose interruptions, fewer dose 
reductions, a reduced usage of growth factor support, and improved relative dose intensity.
As of 13 Jan 2016, in the Part B NHL 3 mg QD schedule cohort, 19 (76.0%) of 25 subjects 
experienced neutropenia, and 16 (64.0%) experienced Grade 3 or 4 neutropenia. In contrast, in 
the Part B DLBCL-2 cohort, 4 mg 5/7 day schedule, 17 (47.2%) of 36 subjects experienced 
neutropenia, and 11 (30.6%) experienced Grade 3 or 4 neutropenia.
Overall, in Part A, 11 (32.4%) out of 34 subjects experienced neutropenia, of which 10 subjects 
(29.4%) experienced Grade 3 or 4 neutropenia. In Part B, 87 (51.5%) out of 169 subjects have 
experienced neutropenia, of which 59 (34.9%) subjects experienced Grade 3 or 4 neutropenia. 
There were no instances of febrile neutropenia in Part A (dose escalation cohorts of the study 
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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
20
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
with doses in the range of 0.5 to 3.5 mg once daily, dosed continuously) and 11 subjects with
febrile neutropenia in Part B.
Doses above the declared 3 mg QD continuous dose MTD and dosing on an intermittent 
schedule are being explored in subjects with GBM. The PCNSL cohort dose and schedule is 4 
mg for 5 out of 7 days, and the MM-2 starting dose is 3 mg for 5 out of 7 days.
During the course of the current study, new formulations of CC-122 were developed and 
evaluated in healthy subjects. Study CC-122-CP-002 Part 2 was an open-label, randomized, 
three-period, six-sequence, three-way single-dose crossover study in healthy adult subjects to 
evaluate the PK of CC-122 after administration of formulated (test formulations: Formulation 4 
[F4] and Formulation 6 [F6]) and non-formulated (reference AIC formulation) CC-122 capsules. 
The formulations have different CC-122 free base amounts compared to the CC-122 active 
ingredient in capsules (AIC) formulation that was employed from the beginning of the current 
study.  CC-122 AIC 0.5, 1, and 3 mg strengths were based on CC-122 HCl and are equivalent to 
0.44, 0.88, and 2.64 mg CC-122 free base, respectively. CC-122 formulated capsules of 1, 3, 3.5 
and 4 mg strengths are based on CC-122 free base and are equivalent to 1.13, 3.38, 3.95 and 4.51 
mg CC-122 HCl, respectively.
Following a single oral administration of CC-122 at the dose level of 3 mg from reference AIC 
formulation and formulated capsule F6 formulation in healthy adult subjects (N=18), the total 
plasma exposure (AUCinf) was 16.29% higher and the peak plasma exposure (Cmax) was 35.58% 
higher from the F6 formulation compared with the reference AIC formulation. The CC-122 F6 
formulation has been selected for further development and within the rest of this protocol is 
referred to as CC-122 formulated capsules. (Data on File, 2015).
Please refer to the Investigator’s Brochure for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event profile of the 
investigational product (IP).
1.2.
Study Rationale/Purpose
CC-122 is a new investigational product that has a strong biological rationale for the treatment of 
subjects with advanced relapsed or refractory cancers, an unmet clinical need. Potential efficacy 
and toxicities associated with CC-122 have been evaluated in preclinical studies and ongoing 
phase 1 studies and provide the scientific rationale for starting clinical development of CC-122 in 
Japan.
This study is the first phase 1 study with this IP in Japan. The primary purpose is to evaluate the 
safety, tolerability, and pharmacokinetics (PK) of CC-122 in Japanese subjects with advanced 
solid tumors or NHL. Preliminary efficacy will be assessed as a secondary objective.
The selected starting dose of 2 mg on a 5 continuous days out of 7 days per week intermittent 
dosing in this study is approximately one-half of the intermittent dose levels (4 and 5 mg on a 5 
continuous days out of 7 days per week intermittent dosing schedule) assessed in the ongoing 
phase 1 study, CC-122-ST-001. Observed toxicity at dose levels up to the MTD of 3 mg QD on a 
continuous dosing schedule and ongoing intermittent dosing schedules had been manageable and 
these dose levels were well tolerated in Western subjects, with fatigue, neutropenia, and diarrhea 
as the most common toxicities, and no DLTs being observed at these dose levels in the 
continuous dosing schedule.
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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
21
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
Based on the mechanism of action of CC-122, and the observed PK and metabolism of the 
compound, as well as reports of no PK differences observed with other similar compounds, 
differences in exposure between Western and Japanese patients are not expected.
Dose levels from 2 mg QD have demonstrated pharmacodynamic effects, including decreased 
peripheral B cells, expansion of peripheral T cells, decreased expression of a CRBN-modulated 
substrate in both B and T cells, and enhanced cytokine expression. The proposed starting dose of 
2 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule is below the 
NTD of 3.5 mg QD and the MTD of 3.0 mg QD in CC-122-ST-001 and is expected to be 
associated with manageable toxicities that can be monitored. Thus, the selected starting dose for 
this study is considered appropriate based on the safety of CC-122 in the ongoing western study 
in subjects with advanced solid tumors and hematologic malignancies and is within the safety 
tolerance established in preclinical toxicology studies.
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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
22
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
2.
STUDY OBJECTIVES
2.1.
Primary Objectives
The primary objectives of the study are:

To determine the safety and tolerability of CC-122 when administered orally to adult 
Japanese subjects with advanced solid tumors or NHL and to define the MTD and/or 
recommended phase 2 dose (RP2D)

To determine the plasma PK of CC-122 in Japanese subjects with advanced solid 
tumors or NHL
2.2.
Secondary Objective
The secondary objective of the study is:

To make a preliminary assessment of the antitumor activity of CC-122
2.3.
Exploratory Objectives
The exploratory objectives of the study are:

To evaluate the plasma PK of CC-122 formulated capsules and compare results to the 
plasma PK of CC-122 AIC

To assess the tolerability of CC-122 formulated capsules

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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
23
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
3.
STUDY ENDPOINTS
3.1.
Primary Endpoint(s)
The primary endpoints of this study are: 

The following safety endpoints: DLTs, MTD, evaluated using the National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria 
version 4.03

PK parameters: Cmax, AUC, Tmax, t1/2, CL/F, Vz/F and Accumulation Index of 
CC-122
3.2.
Secondary Endpoint(s)
The secondary endpoint of this study is:

Antitumor efficacy, determined by response rates in each tumor type using 
appropriate tumor response criteria, and duration of response
3.3.
Exploratory Endpoint(s)
The exploratory endpoints of this study are:

Differences in Cmax and AUCinf between CC-122 AIC and CC-122 formulated 
capsules

Differences in rates of DLTs between formulations

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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
24
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a phase 1, multicenter, open-label, dose-escalation study that will evaluate the safety, 
tolerability, PK, and preliminary efficacy of CC-122 in Japanese subjects with advanced solid 
tumors or NHL.
Subjects will receive ascending dose levels of CC-122 from Cycle 1 onwards to measure PK and 
to determine safety and tolerability.
Figure 1:
Overall Study Design
Screening
Treatment
End of treatment and follow-up
An initial cohort of at least three subjects will be given CC-122 at a dose of 2.0 mg on a 5 
continuous days out of 7 days per week intermittent dosing schedule using AIC. Dose escalation 
for subsequent cohorts will proceed according to a standard dose escalation design (3+3 design) 
(Storer, 1989) to establish initial toxicity.
The provisional dose-escalation levels to be evaluated are as follows.
Table 2:
Provisional Dose-escalation Levels
Cohort
CC-122 dose
Assessed in subjects with solid tumors or NHL
-1
1.0 mg (5 continuous days out of 7 days per week intermittent dosing) using the 
active ingredient in capsule (AIC) formulation
[only used as necessary if the first dose level is not considered tolerable]
1
2.0 mg (5 continuous days out of 7 days per week intermittent dosing) AIC
Assessed only in subjects with NHL
2
3.0 mg (5 continuous days out of 7 days per week intermittent dosing) AIC
Screening 
Eligibility& 
informed consent
signature
(within 28 days of 
Cycle 1 Day 1)
All Cycles (28 days)
CC-122 dosing *
End of treatment 
procedures within 21 days 
of last dose
Follow-up 28 days after last 
dose
* Treatment with CC-122 will continue until clinically significant disease progression, 
unacceptable toxicity or treatment discontinuation for any other reason
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EDMS Doc. Number: 21574111 - 19880032
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
25
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
Table 2:
Provisional Dose-escalation Levels (Continued)
Cohort
CC-122 dose
3
4.0 mg (5 continuous days out of 7 days per week intermittent dosing) AIC
4
3.0 mg (5 continuous days out of 7 days per week intermittent dosing) using the 
formulated capsules
The first dose level will be assessed in subjects with solid tumors or NHL, and subsequent dose 
levels will only be assessed in subjects with NHL.
After at least 3 subjects have been enrolled in the 4 mg CC-122 AIC cohort (Cohort 3) and this 
dose level is determined to be tolerable, at least 6 subjects will be subsequently enrolled in the 
3 mg CC-122 formulated capsules cohort (Cohort 4) to evaluate for differences in PK and 
tolerability. Lower doses using CC-122 formulated capsules may be evaluated as necessary.
4.1.1.
Evaluation of Dose-limiting Toxicities
Cohorts of at least 3 subjects (to 6 subjects) will be enrolled at each dose level.
After the first dose is administered to the last subject in any cohort, subjects are observed for at 
least 28 days (Cycle 1) during the DLT evaluation period before the next higher, protocol-
specified dose level cohort can begin.
A standard escalation schedule will be initiated in order to establish the MTD or RP2D by 
assessing the occurrence of DLTs. Smaller increments and additional subjects within a dose 
cohort may also be evaluated as necessary to determine the MTD and RP2D more precisely.
A dose level will be considered tolerable if 0 of 3 treated subjects experiences a DLT during the 
DLT evaluation period for each respective group. If 1 of 3 subjects experiences a DLT, 3 
additional subjects will be enrolled and treated at that dose level. 
A dose will be considered an NTD when two or more out of six evaluable subjects in a cohort 
experience DLTs during the DLT evaluation period.
The MTD is defined as the last dose level below the NTD with zero or one out of six evaluable 
subjects experiencing DLTs during the DLT evaluation period. At least 6 subjects will be 
enrolled at the MTD/RP2D.
The decision to either evaluate a higher dose level or declare the MTD or RP2D will be 
determined by the Safety Review Committee (SRC), which includes the principal investigator 
and Celgene’s medical monitor (see Section 8.2.1), each time all clinical and laboratory safety 
data for a given cohort are available for review.
The SRC may decide to identify an RP2D based on safety, PK, and preliminary efficacy 
information, which will not exceed the MTD from global CC-122 trials in various indications.
4.2.
Study Design Rationale
The primary objective of this study is to determine the safety, tolerability and PK of oral CC-122
and identify the MTD or RP2D in Japanese subjects with advanced solid tumors or NHL. 
Therefore, a standard phase 1 “3 + 3” dose-escalation design was adopted for this study. The 3 + 
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
3 dose-escalation trial design in this patient population is standard and considered appropriate for 
evaluating the safety and establishing the MTD/RP2D.
Potential efficacy and toxicities associated with CC-122 have been evaluated in preclinical 
studies and ongoing phase 1 studies conducted outside Japan. The dose for CC-122 administered 
in this study was selected according to results from an ongoing phase 1 clinical study, 
CC-122-ST-001 (refer to Section 1.2). The dosing schedules selected are in line with schedules 
proven to be safe and effective in CC-122-ST-001.
4.3.
Study Duration
This study will consist of 3 periods: screening, treatment and end of treatment & follow-up.
During the screening period, lasting up to 28 days, subjects will undergo assessments to 
determine their eligibility. Subjects who qualify for enrollment into the study will enter the 
treatment period. Each subject will be administered oral doses of CC-122 in the treatment period, 
which starts on Cycle 1 Day 1 where IP is administered on a 5 continuous days out of 7 days per 
week intermittent dosing schedule (Cycle = 28 days).
If subjects continue therapy with CC-122, subsequent cycles are 28 days long on a 5 continuous 
days out of 7 days per week intermittent dosing schedule.
Subjects may continue CC-122 without interruption for as long as they derive benefit, as 
assessed by the investigator. Treatment will be discontinued if there is evidence of clinical 
significant disease progression, unacceptable toxicity or if the subject/physician decides to stop 
treatment.
The follow-up period will begin at the discontinuation of IP treatment. Subjects will have an end
of treatment (EOT) assessment during an evaluation within 21 days of the last dose of IP and a 
follow-up visit 28 days after the last dose of IP to obtain information regarding new or ongoing 
AEs.
4.4.
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as prespecified in the protocol and/or the 
Statistical Analysis Plan, whichever is the later date.
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
5.
TABLE OF EVENTS
The following table lists all of the assessments and indicates with an “X” the visits when they are performed. More frequent 
examinations may be performed at the investigator’s discretion if medically indicated, and clinically significant results should be 
recorded on Unscheduled Visit case report forms (CRFs). All data obtained from these assessments must be supported in the subject’s 
source documentation.
After completion of Cycle 1, written informed consent will be obtained again from subjects prior to the start of the second cycle of 
treatment.
Subjects will be hospitalized during the DLT evaluation period (Cycle 1) as a rule. 
Table 3:
Table of Events
Test and Observations
Reference 
Section
Screening
Treatment cycles (28 days)
End of 
treatment Follow-up
Cycle 1
Cycle 2 to 4
Subsequent 
Cycles *
Visit
(Allowable window)
Within 
28 days 
of Cycle 
1 Day 1
Within 7 
days of 
Cycle 1 
Day 1
Day 1 Day 2
Day 8
(± 2 
days)
Day 
10, 11 
or 12
Day 
11, 12 
or 13
Day 
15
(± 2 
days)
Day 
22
(± 2
days)
Day 1
(± 2 
days) a
Day 8
(± 2 
days)
Day 
15
(± 2 
days)
Day
22
(± 2 
days)
Day 1
(± 3 days)
Within 21 
days of 
last dose
28 days
after last 
dose
(+ 7 days)
Informed consent
6.1.1
X
X b
Demography
6.1.2
X
Inclusion/Exclusion criteria
7.2, 7.3
X
Complete medical history
6.1.2
X
Prior therapies
6.1.2
X
Diagnosis and extent of 
cancer
6.1.2
X
Concomitant medications & 
procedures
6.1.4
X
Physical examination
6.2.1
X
X
X
X
X
ECOG Performance status
6.2.3
X
X
X
X
X
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
Table 3:
Table of Events (Continued)
Test and Observations
Reference 
Section
Screening
Treatment cycles (28 days)
End of 
treatment Follow-up
Cycle 1
Cycle 2 to 4
Subsequent 
Cycles
Visit
(Allowable window)
Within 
28 days 
of Cycle 
1 Day 1
Within 7 
days of 
Cycle 1 
Day 1
Day 1 Day 2
Day 8
(± 2 
days)
Day 
10, 11 
or 12
Day 
11, 12 
or 13
Day 
15
(± 2 
days)
Day 22
(± 2 
days)
Day 1
(± 2 
days) a
Day 8
(± 2 
days)
Day 
15
(± 2 
days)
Day
22
(± 2 
days)
Day 1
(± 3 days)
Within
21 days 
of last 
dose
28 days
after last 
dose
(+ 7 days)
Assessment of hydration 
status
6.2.1
X
X
X
X
X
X
X
X
X
X
Height
6.2.1
X
Weight
6.2.1
X
X
X
X
X
X
X
X
X
X
X
Vital signs
6.2.2
X
X
X
X
X
X
X
X
X
X
X
Serum β-HCG pregnancy test 
(for FCBP only) c
6.2.4
X c
As clinically indicated
Urine β-HCG pregnancy test
(for FCBP only) c
6.2.4
X
X
X
X
X
X
X
X
Amylase, lipase
6.2.6
X
X
X
X
Cholesterol & TG
6.2.6
X
X
X
X
TSH, fT4, LDH
6.2.6
X
X
X
X
Immunoglobulins & T cell 
subsets (CD4+, CD8+)
6.2.6
X
X
X
X
Uric acid
6.2.6
X
X
X
X
Troponin-T, BNP
6.2.6
X
X d
X
X
X
X
X
X
Hematology with differential
6.2.6
X
X d
X
X
X
X
X
X
X
X
X
X
Biochemistry
6.2.6
X
X d
X
X
X
X
X
X
X
X
X
Coagulation
6.2.6
X
X d
X
X
X
X
X
X
X
X
X
Urinalysis
6.2.6
X
X d
X
X
X
HBsAg & HCV RNA
6.2.6
X
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Table 3:
Table of Events (Continued)
Test and Observations
Reference 
Section
Screening
Treatment cycles (28 days)
End of 
treatment Follow-up
Cycle 1
Cycle 2 to 4
Subsequent 
Cycles
Visit
(Allowable window)
Within 
28 days 
of Cycle 
1 Day 1
Within 7 
days of 
Cycle 1 
Day 1
Day 1 Day 2
Day 8
(± 2 
days)
Day 
10, 11 
or 12
Day 
11, 12 
or 13
Day 
15
(± 2 
days)
Day 22
(± 2 
days)
Day 1
(± 2 
days) a
Day 8
(± 2 
days)
Day 
15
(± 2 
days)
Day
22
(± 2 
days)
Day 1
(± 3 days)
Within 21 
days of 
last dose
28 days
after last 
dose
(+ 7 days)
12-lead ECG e
6.2.7.1
X
X
X
X
X
X
X
X
X
X
X
X
LVEF (MUGA or ECHO) f
6.2.7.2
X
X f
X f
X
Ophthalmologic examination g
6.2.8
X
Tumor assessments h
6.3
X
X h
Day 15
instead of 
Day 1
X h
X
PK sampling i
6.4
X
X
X
X
CC-122 contraceptive risk 
counseling and education
6.2.5
To be completed prior to each dispensing of IP as per PPRMP
X
Dispense CC-122
8.1, 8.2
X
X
X
Drug 
accountability/compliance
8.5, 8.6
X
X
X
CC-122 administration (5 out 
of 7 day dosing) j
8.2
X
X
X
X
X k
X
X
X
X
X
X
X
AE monitoring
11
X l
AE = adverse event; BNP = brain natriuretic peptide; C = cycle; CD = cluster of differentiation; CT = computed tomography; D = day; ECG = electrocardiogram; ECHO = 
echocardiogram; ECOG = Eastern Cooperative Oncology Group; FCBP = females of childbearing potential; fT4 = free thyroxine 4; HBsAg = Hepatitis B surface antigen; HCG 
= Human chorionic gonadotropin; HCV = Hepatitis C virus; IP = investigational product; LDH = lactate dehydrogenase; LVEF = left ventricular ejection fraction; MRI = 
magnetic resonance imaging; MUGA = multiple gated acquisition scan; PK = pharmacokinetic; PPRMP = Pregnancy Prevention Risk Management Plan (Appendix B, Section 
19.2); RNA = ribonucleic acid; TG = triglycerides; TSH = thyroid stimulating hormone.
* With Protocol Amendment 03, Day 8 and 22 visits from Cycle 5 onwards and Day 15 visits from Cycle 5 onwards were eliminated, with the exception of Day 15 of Cycle 6 and 
every 3 cycles thereafter for tumor assessments. Subjects enrolled prior to this protocol amendment may have data at these visits prior to the approval of protocol amendment 03.
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
a The ±2 day allowable window does not apply to Cycle 2 Day 1.
b After completion of Cycle 1, written informed consent will be obtained again from subjects prior to the start of the second cycle of treatment.
c As per the PPRMP, screening pregnancy tests must be performed within 10 to 14 days prior to starting dosing. FCBP with regular or no menstrual cycles will undergo postdose 
pregnancy tests as noted on this table, every week for the first 28 days and every 28 days thereafter until the end of treatment, and 28 days after the last dose of CC-122. However, 
FCBP with irregular menstrual cycles will undergo weekly assessments for the first 28 days, every 14 days thereafter until the end of treatment and the end of treatment 
pregnancy test must be performed 14 and 28 days after discontinuing treatment.
d If screening assessments are performed within 2 days of Cycle 1 Day 1 these assessments do not need to be repeated on Cycle 1 Day 1.
e Triplicate ECGs (3 recordings within 2±1 minute intervals) will be performed only at screening. Single ECGs will be collected for all other visits.
f During the study, LVEF assessments should be repeated on Day 1 after every three cycles starting with Cycle 3 and when clinically indicated (for example, for decreased cardiac 
output) using the same modality at screening.
g Ophthalmology examinations will be performed for all subjects at screening and during the study if clinically indicated.
h Tumor assessments include imaging studies (via CT/MRI) and may include brain scans, and/or bone marrow aspirate/biopsy depending on tumor type and involvement. After 
screening, tumor assessments will be performed on Day 15 of Cycle 2, 4, 6 and every 3 cycles thereafter (Cycles 9, 12, 15, etc.), with an allowable window of ±7 days. Tumor 
assessments at the end of treatment visit may be omitted if performed within the previous 28 days.
i Refer to Section 6.4 for details on PK sampling time points.
j Starting from Cycle 1 Day 1, CC-122 is administered once a day for 5 continuous days out of 7 days per week.
k If performed on Day 13, a dose of CC-122 will not be administered.
l AE monitoring will be performed according to Section 11 and AEs will be followed for up to 28 days after the last dose of IP. However, AE monitoring for non-serious AEs may 
be halted once other anticancer treatments are started even if the full 28 days of follow-up has not been completed.
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
6.
PROCEDURES
Procedures will be performed at the visits listed in Table 3.
6.1.
Screening Assessments
6.1.1.
Informed Consent
The screening period begins on the date the Informed Consent Form (ICF) is signed and should 
be within 28 days of Cycle 1 Day 1. The ICF must be signed and dated by the subject and the 
administering staff prior to the start of any study procedures solely for the purpose of this study 
and completion documented in source documents and the CRF. Standard of care assessments 
performed prior to signing the ICF may be used for this study, assuming these assessments meet 
the protocol requirements. Recording of Adverse AEs/Serious adverse events (SAEs) will begin 
once the subject has signed the ICF.
Written informed consent will be obtained again from subjects prior to the start of the second 
cycle of treatment.
6.1.2.
Patient Demographics/Medical History/Diagnosis and Extent of Cancer/Prior 
Therapies
Medical, surgical and oncologic histories, diagnosis and extent of cancer, along with 
demographic data, including each subject’s date of birth, gender, race, and ethnicity will be 
collected during screening as consistent with local regulations. The medical history will be 
general enough to document common co-morbid conditions as well as specific enough to reveal 
any conditions listed as participation exclusion criteria, and will document whether the identified 
conditions are active or inactive at the time of enrollment. All prior anticancer treatments (for 
example, chemotherapy, surgeries) and medical history, including approximate dates of 
treatment or diagnosis, must be recorded during screening. This should be recorded in source 
documents and the CRF.
6.1.3.
Assessment of Inclusion/Exclusion Criteria
Inclusion and exclusion criteria will be assessed at screening and recorded in source documents 
and the CRF.
6.1.4.
Concomitant Medications and Procedures
All concomitant medications and procedures taken or performed beginning 28 days prior to the
administration of IP until 28 days after the last dose of IP will be recorded in the source 
documents and the CRF.
6.1.5.
Information to be Collected on Screen Failures and Non-treated Subjects
The following are minimum data requirements to be entered in CRFs for screen failures and 
other subjects who did not start treatment.

Subject number
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
Date of informed consent

Demography

Screening visit date

Eligibility criteria – specific inclusion and/or exclusion criteria not met by the subject, 
as applicable

All AEs/SAEs from the time of signing the ICF until discontinuation from study

Disposition – the date when it was determined that the subject would not continue 
further in the study, and specification of the reason for termination from the study 
(“Screen Failure” for subjects who do not meet all of the eligibility criteria, or the 
applicable reason for other non-treated subjects)
6.2.
Safety Assessments
6.2.1.
Physical Examination, Height and Weight, Assessment of Hydration Status
Complete physical examinations, assessments of hydration status, and measurements of height 
and weight will be performed at the visits listed in Table 3. Assessments of hydration status 
should be performed and recommendations for per os (PO) or intravenous (IV) hydration given 
as applicable.
Results of physical examinations and assessment of hydration status will be recorded in source 
documents and height and weight recorded on source documents and the CRF.
6.2.2.
Vital Signs
Vital signs include body temperature, blood pressure, pulse rate, and respiration rate. Recorded 
measurements will be captured in the source documents and the CRF.
Vital signs should be measured after the subject has rested for at least 5 minutes. Vital sign 
measurements should be repeated for confirmation if clinically significant observations or 
changes from baseline occur. All confirmed, clinically significant vital sign measurements must 
be recorded as AEs.
6.2.3.
Eastern Cooperative Oncology Group Performance Status
Performance status will be assessed using the following scale. Data will be captured in the source 
documents and the CRF.
Table 4:
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, for example, 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
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
Table 4:
ECOG Performance status Scale (Continued)
Score
Description
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
6.2.4.
Pregnancy Test
A female of child bearing potential (FCBP) is defined as a female who has:
1. Achieved menarche at some point
2. Not undergone a hysterectomy or bilateral oophorectomy, or
3. Not been naturally postmenopausal (amenorrhea following cancer therapy does not rule 
out childbearing potential) for at least 24 consecutive months (has had menses at any time 
in the preceding 24 consecutive months).
The investigator will classify a female subject as an FCBP according to this definition. 
Pregnancy testing is not required for non-FCBP subjects but justification must be recorded in the 
CRF and source documents. Pregnancy testing will be conducted by the local laboratory.
For an FCBP, pregnancy testing will be conducted at the visits listed in Table 3:

A serum pregnancy test with sensitivity of at least 25 mIU/mL is to be obtained at 
screening.

A urine pregnancy test (minimum test sensitivity [25 mIU/mL]) should be performed 
at subsequent visits; however, a serum pregnancy test may be performed as clinically 
indicated.

The subject may not receive IP until the investigator has verified the screening 
pregnancy tests to be negative.

An FCBP must avoid activities that could lead to conception for 28 days after the last 
dose of any IP or a male subject whose partner is an FCBP must avoid activities that 
could lead to conception within 3 months after the last dose of CC-122.
Note: FCBP receiving CC-122 will undergo pregnancy testing according to the schedule 
described in the CC-122 Pregnancy Prevention Risk Management Plan and CC-122 Information 
Sheet.
Results for pregnancy tests will be recorded in source documents and CRFs.
6.2.5.
Contraceptive Counseling
Subjects will be counseled about appropriate contraception during screening (refer also to the 
previous section). Double contraceptive methods (one of which must be a barrier method) for 
females (such as oral, injectable, or implantable hormonal contraceptives; intra-uterine devices; 
barrier contraceptives with spermicide approved or certified in Japan; or a vasectomized partner) 
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
and a single contraceptive method for males (complete abstinence or a condom) must be used 
from the time the ICF is signed, throughout the study by fertile subjects, and for 28 days after the 
last dose of IP for FCBP and for 3 months after the last dose of CC-122 for male subjects whose 
partner is an FCBP. FCBP must confirm that they have been using appropriate contraception for 
at least 28 days prior to starting CC-122 as per the PPRMP. Counseling should be documented in 
source documents.
The CC-122 PPRMP for Celgene Clinical Trials applies to all subjects receiving CC-122 therapy 
and will be given to sites as a separate document.
CC-122 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, 
or designee, in requirements specific to counseling of subjects. Once trained, these healthcare 
staff will counsel subjects prior to the administration of CC-122 to ensure that the subject has 
complied with all requirements, including use of birth control, and that the subject understands 
the risks associated with CC-122. This step will be documented with a completed Education and 
Counseling Guidance Document, and CC-122 will not be administered until this step occurs.
A CC-122 Information Sheet will be provided to each subject before IP is dispensed.
Females of childbearing potential and fertile males, other than the subject, should not handle or 
administer CC-122 unless they are wearing gloves.
6.2.6.
Clinical Laboratory Tests
The following clinical laboratory tests will be assessed. All samples should be drawn predose 
unless otherwise specified. Data will be captured in the source documents and the CRF.
Table 5:
Clinical Laboratory Test Parameters
Laboratory test
Parameters
Amylase, lipase
Amylase, lipase
Cholesterol and 
triglycerides
Cholesterol and triglycerides
Thyroid stimulating 
hormone (TSH), free 
thyroxine 4 (fT4), and 
lactate dehydrogenase 
(LDH)
TSH, fT4, and LDH
Immunoglobulins (Ig) 
and 
T cell subsets
Immunoglobulins = IgG, IgM and IgA only
T cell subsets = CD4+ and CD8+
Uric acid
Uric acid
Troponin-T, brain 
natriuretic peptide (BNP)
Troponin-T, BNP
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CC-122
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Celgene K.K.
Confidential and Proprietary
35
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
Table 5:
Clinical Laboratory Test Parameters (Continued)
Laboratory test
Parameters
Hematology
Complete blood count consisting of red blood cells (RBCs), a total white 
blood cell count with differentials (including total neutrophil [including 
bands], lymphocyte, monocyte, eosinophil, and basophil counts), 
hemoglobin, hematocrit and platelet count
Biochemistry
Sodium, potassium, chloride, calcium, glucose, magnesium, phosphorus, 
serum blood urea nitrogen (BUN), serum creatinine, total bilirubin, 
aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
alkaline phosphatase, albumin, and total protein
Coagulation
Prothrombin time (PT), international normalized ratio (INR) and, partial 
thromboplastin time (PTT)
Urinalysis
Dipstick test, with microscopy in event of positive (1+ or greater) blood or 
protein and 24-hour collection for creatinine clearance and protein 
quantification in the event of 2+ or greater protein
HBsAg and HCV RNA
Hepatitis B surface antigen (HBsAg) & Hepatitis C virus (HCV) 
ribonucleic acid (RNA)
If Hepatitis B core antibody (HBcAb) and/or Hepatitis B surface antibody 
(HBsAb) is positive even if HBs antigen is negative, measurement of 
hepatitis B viral load (HBV DNA quantitated by PCR) should be 
performed and, if positive, the subject will be excluded from the study
6.2.7.
Cardiac Imaging
6.2.7.1.
12-lead Electrocardiograms
Triplicate or single standard 12-lead electrocardiograms (ECGs) will be recorded. The 12-lead 
ECGs (12-lead at 25 mm/sec reporting rhythm, ventricular rate, PR-interval, QRS complex, QT 
interval, and corrected QT [QTc] interval) will be performed after the subject has been in the 
supine position for at least 5 minutes. Data will be captured in the source documents and the 
CRF.
Whenever vital signs, ECGs and/or blood draws are scheduled for the same nominal time, the 
ECG will be obtained first, followed by vital signs and then blood draw(s).
6.2.7.2.
Left Ventricular Ejection Fraction
LVEF will be measured via multiple gated acquisition scan (MUGA), or echocardiogram 
(ECHO) for all subjects. Follow-up assessments should use the same procedure used at the 
screening assessment. Data will be captured in the source documents and the CRF.
6.2.8.
Ophthalmologic Examination
An ophthalmologic examination will be performed by a qualified ophthalmologist at screening as 
described below in all subjects. The screening ophthalmologic exam will include:

Visual acuity
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016

Slit-lamp examination with fluorescein staining following pupillary dilation (unless 
fluorescein and pupillary dilatation are contraindicated)

Ophthalmologic examination focusing on the anterior chamber, iris and anterior 
vitreous
Subsequent ophthalmologic examinations will be performed as clinically indicated. If there are 
any clinically significant findings, a full ophthalmologic exam will be conducted by a qualified 
ophthalmologist.
6.3.
Efficacy Assessments
Tumor assessments will be performed as follows:
Table 6:
Tumor Assessments
Visit
Assessments
Screening
Tumor assessments via imaging studies, including computed 
tomography (CT) and/or magnetic resonance imaging (MRI), of 
the chest and abdomen and pelvis (including other sites, as 
appropriate) [or fludeoxyglucose positron emission tomography 
(FDG-PET) as necessary] will be performed.
A brain scan (CT or MRI) will be performed for subjects with 
known brain lesions.
Bone marrow aspirate and biopsy (with cytogenetic analysis, as 
appropriate depending on cancer type) should be performed for 
subjects with known or suspected bone marrow involvement.
Note: Efficacy assessments (scans, aspirates, and biopsies) obtained 
within 8 weeks of the first dose of IP and prior to obtaining informed 
consent as part of standard of care assessments may be used, assuming 
these assessments meet the protocol requirements.
Day 15 of Cycle 2, 4, 6 and 
every 3 cycles thereafter 
(Cycles 9, 12, 15, etc.)
Allowable window: (± 7 days)
Tumor assessments via imaging studies, including CT and/or 
MRI, of the chest and abdomen and pelvis (including other sites, 
as appropriate) [or FDG-PET as necessary] will be performed.
A brain scan (CT or MRI) will be performed for subjects with 
known brain lesions.
Bone marrow aspirate and biopsy (with cytogenetic analysis, as 
appropriate depending on cancer type) should be performed for 
subjects with known or suspected bone marrow involvement.
End of treatment
(may be omitted if performed 
within the previous 28 days)
Tumor assessments via imaging studies, including CT and/or 
MRI, of the chest and abdomen and pelvis (including other sites, 
as appropriate) [or FDG-PET as necessary] will be performed.
A brain scan (CT or MRI) will be performed for subjects with 
known brain lesions.
Bone marrow aspirate and biopsy (with cytogenetic analysis, as 
appropriate depending on cancer type) should be performed for 
subjects with known or suspected bone marrow involvement.
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Celgene K.K.
Confidential and Proprietary
37
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
After screening, tumor assessments thereafter should be performed using the same CT/MRI 
scanning modalities used at screening, as permissible.
6.4.
Pharmacokinetic Assessments
The schedule for PK assessments is described below:
Table 7:
PK Sampling Time Points
Visit
Nominal time point
Allowable window
Cycle 1 Day 1
Predose
<15 min prior to dosing
0.5 hours postdose
± 5 minutes
0.75 hours postdose
± 5 minutes
1 hour postdose
± 5 minutes
1.5 hours postdose
± 5 minutes
3 hours postdose
± 10 minutes
5 hours postdose
± 10 minutes
8 hours postdose
± 10 minutes
Cycle 1 Day 2
24 hours after dose administered on Cycle 1 
Day 1 and predose of dosing on Cycle 1 Day 
2
<15 min prior to dosing
Cycle 1 Day 10, 11 or 
12
Predose
<15 min prior to dosing
0.5 hours postdose
± 5 minutes
0.75 hours postdose
± 5 minutes
1 hour postdose
± 5 minutes
1.5 hours postdose
± 5 minutes
3 hours postdose
± 10 minutes
5 hours postdose
± 10 minutes
8 hours postdose
± 10 minutes
Cycle 1 Day 11, 12 or 
13
24 hours after dose administered on Cycle 1 
Day 10, 11 or 12 and predose of dosing on 
Cycle 1 Day 11, 12 or 13
± 1 hour
Should dose administration CC-122 be interrupted for > 72 hours before the Cycle 1 Day 10, 11 
or 12 sampling, serial PK samples will not be collected until ≥ 2 days of CC-122 continuous 
treatment has been reestablished.
Intra-subject dose escalation:
The following additional PK samples will only be collected for subjects who were dose escalated 
from their initial assigned dose (see Sections 8.2.1 and 8.2.9.2):
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016

After at least 2 days of continuous dosing of CC-122, PK samples should be collected 
at the following time points:

At predose (<15 min prior to dosing), and at 0.5, 0.75, 1, 1.5, 3, 5, 8, and 24 hours 
postdose
Sample collection kits and detailed instructions for PK sample collection, processing, storage, 
shipping and handling will be provided to the sites by the central laboratory upon study initiation.
 
 
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Approximately 15 subjects will be enrolled and treated in approximately 3 sites in Japan.
However, the total number of subjects enrolled will depend on the number of dose cohorts 
needed to establish the MTD/RP2D.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Understand and voluntarily sign an informed consent document prior to any study-related 
assessments/procedures are conducted
2. Men and women, 20 years or older, with histological or cytological confirmation of
advanced solid tumors or NHL, including those who have progressed on (or are not able 
to tolerate) standard anticancer therapy or for whom no other conventional therapy exists
(Note: subjects with solid tumors or NHL will be enrolled for the first dose level and 
only subjects with NHL will be enrolled in subsequent dose levels)
3. ECOG Performance Status ≤ 2 for all tumors
4. Subjects must have the following laboratory values:

Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

Hemoglobin (Hgb) ≥ 9 g/dL, drawn at least 7 days after the last RBC transfusion

Platelets (Plt) ≥ 100 x 109/L, drawn at least 7 days after the last platelet transfusion

Potassium within normal limits or correctable with supplements

AST and ALT ≤ 3 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver tumors are
present

Serum bilirubin ≤ 1.5 x ULN; subjects with serum bilirubin >1.5 x ULN and ≤ 2 x
ULN may be enrolled if agreed to by the sponsor

Serum creatinine ≤ ULN or 24-hour clearance ≥ 50 mL/min

Negative serum pregnancy test in females of childbearing potential as per the CC-122
PPRMP (Appendix B, Section 19.2)
5. Able to adhere to the study visit schedule and other protocol requirements
6. Must adhere to the PPRMP
a.
Females of childbearing potential must undergo pregnancy testing based on the 
frequency outlined in PPRMP and pregnancy results must be negative
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Confidential and Proprietary
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
b. Unless practicing complete abstinence from heterosexual intercourse, sexually active
FCBP must agree to use adequate contraceptive methods as specified in the PPRMP

Complete abstinence is only acceptable in cases where this is the preferred and
usual lifestyle of the subject.

Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable
c.
Males (including those who have had a vasectomy) must practice complete 
abstinence or use barrier contraception (condoms) when engaging in sexual activity 
with FCBP as specified in the PPRMP
d. Males must agree not to donate semen or sperm for the duration specified in the 
PPRMP
e.
All subjects must:

Understand that the IP could have a potential teratogenic risk.

Agree to abstain from donating blood while taking IP and following
discontinuation of investigational product.

Agree not to share IP with another person.
f.
Other than the subject, FCBP and males able to father a child should not handle the IP
or touch the capsules, unless gloves are worn
g. Be counseled about pregnancy precautions and risks of fetal exposure
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Subjects with primary central nervous system (CNS) malignancies or symptomatic 
central nervous system metastases. Subjects with brain metastases that have been 
previously treated and are stable for 6 weeks are allowed
2. Known acute or chronic pancreatitis
3. Any peripheral neuropathy ≥ NCI CTCAE Grade 2
4. Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical
management
5. Impaired cardiac function or clinically significant cardiac diseases, including any of the
following:

LVEF < 45% as determined by MUGA scan or ECHO

Complete left bundle branch, or bifascicular block

Congenital long QT syndrome

Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation

QTcF > 460 msec on screening ECG (mean of triplicate recordings)

Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting CC-122
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
Troponin-T value >0.4 ng/mL or BNP >300 pg/mL
Subjects with baseline troponin-T >ULN or BNP >100 pg/mL are eligible but must 
have cardiologist evaluation prior to enrollment in the trial for baseline assessment 
and optimization of cardioprotective therapy.

Other clinically significant heart disease such as congestive heart failure requiring
treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mmHg)
6. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 
weeks, whichever is shorter, prior to starting CC-122 or who have not recovered from 
side effects of such therapy. Luteinizing hormone-releasing hormone (LHRH) agonists 
will be allowed for subjects with metastatic prostate cancer
7. Major surgery ≤ 2 weeks prior to starting CC-122 or still recovering from post operative 
side effects
8. Women who are pregnant or breast feeding. Adults of reproductive potential not
employing two forms of birth control as per PPRMP
9. Known human immunodeficiency virus (HIV) infection *
10. Known acute or chronic hepatitis B or C virus infection **
11. Status post solid organ transplant
12. Less than 100 days for subjects receiving autologous hematologic stem cell transplant
(HSCT); or 6 months for subjects receiving allogeneic HSCT, or if otherwise not fully
recovered from HSCT-related toxicity
a.
The 6-month exclusionary period for recovery from HSCT-associated toxicity,
applies regardless of whether an autologous or allogeneic transplant was performed
13. Known hypersensitivity to any component of the formulation of CC-122
14. Any significant medical condition (including active or controlled infection or renal 
disease), laboratory abnormality, or psychiatric illness that would prevent the subject 
from participating in the study
15. Any condition, including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study
16. Any condition that confounds the ability to interpret data from the study
* HIV testing is not required at screening.
** Refer to Table 5 for exclusion based on hepatitis testing results.
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8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Product(s)
Please refer to the CC-122 Investigator’s Brochure for detailed information concerning the
physical properties of CC-122.
CC-122 will be supplied in two distinct formulations as follows: CC-122 AIC in 0.5, 1 and 3-mg 
strengths (equivalent to 0.44, 0.88, and 2.64 mg free base CC-122, respectively) and as CC-122 
formulated capsules in 1, 3, 3.5 and 4-mg strengths (equivalent to 1.13, 3.38, 3.95 and 4.51 mg 
CC-122 HCl, respectively).
CC-122 AIC will be provided in white/white opaque gelatin capsules in strengths of 0.5 mg 
(size 4), 1 mg (size 3), and 3 mg (size 2). There are no excipients in the capsules.
The formulated capsules will be provided in reddish brown gelatin capsules in strengths of 1 mg 
(size 3), 3 (size 3), 3.5 mg (size 2) and 4 mg (size 2), containing the following excipients: Avicel 
PH 102, spray dried mannitol, crospovidone, areosil, and stearic acid.
The IP will be labeled per local regulations. Store as directed on the package label.
8.2.
Treatment Administration and Schedule
CC-122 is administered orally, on a 5 continuous days out of 7 days per week intermittent dosing 
schedule.
Each dose will be taken in the morning, with the subject having fasted overnight (minimum of 6 
hours) and for one hour after dosing. Every effort should be made to ensure that subjects are 
adequately hydrated prior to dosing, such as ensuring that capsules are swallowed with at least 8 
ounces of water (approximately 240 mL), and hydration levels should be adjusted according to 
age and clinical status.
Breakfast will be delayed until at least one hour after dosing. The site will record the time of the 
first meal after dosing for clinic visits with PK collection time points.
Doses will be administered in an escalating manner following satisfactory review of safety data 
from the lower doses. Within each cohort, enrollment will be staggered 24 hours or more 
between Cycle 1 Day 1 visits for each subject.
8.2.1.
Safety Review Committee
The SRC will review the safety and available PK data at the end of the DLT evaluation period
for each cohort to determine whether dose escalation can occur, to confirm the dose level to be 
used in a subsequent cohort, and to determine the MTD/RP2D. The SRC will also review and 
approve intra-subject dose escalations.
SRC members will include the study investigators, the sponsor’s medical monitor, safety 
physician or designee, clinical research scientist, and study manager. In addition, the study 
pharmacokineticist, statistician, and other relevant study team members may attend, if needed, 
and both internal and external experts may be consulted by the SRC, as necessary. The outcomes 
of SRC meetings will be documented, and the minutes distributed for SRC approval.
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8.2.2.
Definition of a Treatment Cycle
Each subject will be administered oral doses of CC-122 starting from Cycle Day 1 on a 5 
continuous days out of 7 days per week intermittent dosing schedule in 28-day cycles (DLT 
evaluation period = at least 28 days).
Subjects may continue to receive CC-122 for as long as they derive benefit from treatment as 
assessed by the investigator. In subsequent cycles, subjects are treated in 28-day cycles on a 5 
continuous days out of 7 days per week intermittent dosing schedule.
8.2.3.
Starting Dose Level and Provisional Dose Levels
The starting dose is a flat dose of 2.0 mg administered on a 5 continuous days out of 7 days per 
week intermittent dosing schedule. Provisional dose-escalation levels are listed in Table 2.
8.2.4.
Definition of Evaluable Subjects
A subject evaluable for DLT evaluation is defined as one whom, in the DLT evaluation period, 
either:
a.
Received at least 85% of the planned doses of CC-122 at the cohort-specified dose in 
Cycle 1 (at least 17 out of 20 doses for the 5 continuous days out of 7 days per week
intermittent dosing cohorts), has sufficient data for safety evaluation by the SRC and 
has not experienced a treatment-related DLT, or
b. Received at least one dose of CC-122 and experienced a DLT
Non-evaluable subjects will be replaced in the dosing cohort. An additional subject may be 
enrolled in each dosing cohort to allow for early drop-outs and to avoid study delays after 
consultation with the sponsor.
Subjects for whom >20% of PK samples were not collected will also be replaced in order to 
collect sufficient data for PK analysis.
8.2.5.
Definition of Maximum Tolerated Dose and Non-tolerated Dose
The non-tolerated dose is defined as the dose level at which 2 or more out of 6 evaluable subjects 
in any dose cohort experience a DLT.
Once the NTD is identified, dose escalation will be halted.
The MTD is defined as the last dose level below the NTD with zero or one (out of 6) evaluable 
subject experiencing DLTs during the DLT evaluation period. An intermediate dose (for 
example, one between the NTD and the last dose level before the NTD) or additional subjects 
within a dose cohort may be evaluated in order to determine the MTD more precisely.
8.2.6.
Definition of Dose-limiting Toxicities
National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 will 
be used to grade adverse events. Events described below will be classified as DLTs.
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Table 8:
DLT Criteria
Toxicity
Non-hematologic AEs
A clinically relevant non-hematologic AE that is suspected to be 
related to CC-122 and that commences during the DLT evaluation 
period and is ≥ Grade 3 EXCEPT for:

Grade 3 rash of the acneiform or maculopapular type lasting ≤ 4 
days (with optimal medical management)

Grade 3 diarrhea or vomiting lasting less than 72 hours (with 
optimal medical management)
Laboratory abnormalities
A clinically relevant laboratory abnormality that is suspected to be 
related to CC-122 and that commences during the DLT evaluation 
period and is ≥ Grade 3
Hematologic
Any febrile neutropenia
Grade 4 neutropenia lasting > 7 days
Grade 4 thrombocytopenia lasting > 24 hours or thrombocytopenia of 
any grade requiring platelet transfusions
Any Grade 3/4 thrombocytopenia with clinically significant bleeding
Hepatic
Grade 4 liver function tests (LFTs) or Grade 3 ALT with Grade 2 or 
higher bilirubin will be considered a DLT, irrespective of underlying 
attribution
However, other Grade 3 LFTs due to disease progression in the liver 
will not be considered DLTs
Other adverse events
Any adverse event suspected to be related to CC-122 and 
necessitating a dose reduction during the DLT evaluation period
Toxicities will be considered treatment-related unless clearly attributed to an alternative etiology 
(for example, tumor progression) by the investigator. Toxicities must be clearly not related to 
disease progression, medical procedures or intercurrent illnesses in order to be considered dose-
limiting.
Isolated laboratory changes without associated clinical signs or symptoms will not be included in 
this definition. These findings will be discussed and reviewed by the SRC.
8.2.7.
Criteria for Dose Escalation in the Next Cohort of Subjects
Cohorts will consist of at least 3 or at least 6 evaluable subjects. The decision criteria for dose 
escalation in any cohort are:

If no DLT is observed in at least 3 evaluable subjects during the first cycle, the dose 
will be considered a well-tolerated dose and dose escalation will continue to the next 
dose level.

If any DLT is observed in 2 or more of 6 evaluable subjects in the cohort, this dose is 
considered a non-tolerated dose and dose escalation will discontinue.
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
If any DLT is observed in one evaluable subject during the DLT evaluation period, 
additional subjects will be enrolled to expand the cohort to up to at least 6 evaluable 
subjects.
The number of cohorts depends on the incidence of DLTs. A subject may experience more than 
one DLT. Dose-escalation decisions are based on the number of subjects experiencing DLTs.
8.2.8.
Definition of Stopping Criteria for Dose Escalation
Dose escalation stops when 2 or more of 6 evaluable subjects at a dose level experience DLTs or 
the MTD in global CC-122 studies in various indications has been reached.
8.2.9.
Permitted Dosing Adjustments
No dose reduction is allowed during the DLT evaluation period, except for subjects who 
experience DLTs. Subjects who experience DLTs during the DLT evaluation period will be 
allowed to resume CC-122 at a reduced dose once their toxicity recovers to Grade 1 or baseline,
provided recovery occurs within 28 days of interrupting dosing. Dose reductions for non-dose-
limiting toxicities are allowed after the DLT evaluation period after consultation with the 
sponsor.
Those continuing to take CC-122 beyond Cycle 1 may, following approval by the SRC, have 
their dose level increased, provided that the alternative dose level has been shown to be well-
tolerated in at least one cohort of other subjects in this study. In these instances, additional PK 
evaluations at the higher dose level will be collected.
If a dose reduction is indicated, the next lower dose level will be selected. Two dose reductions 
are allowed, with the exception of the starting dose for which only one dose reduction is allowed. 
If any subject continues to experience unacceptable toxicity after 2 dose reductions, CC-122 will 
be discontinued permanently.
8.2.9.1.
Criteria for Dose Reduction
Dose reductions are not allowed during the DLT evaluation period, except for subjects who 
experience DLTs. Subjects who experience toxicities during the DLT evaluation period that do 
not meet the protocol specified definition for DLTs (Section 8.2.6) may either continue at their 
assigned dose or withdraw from the study at the discretion of the investigator and/or the subject. 
If a subject withdraws for any reason other than DLTs prior to the completion of the DLT 
evaluation period, that subject will be considered non-evaluable and will be replaced.
Once the dosage has been reduced for toxicity for a subject, future escalation will not be 
permitted.
Any of the AEs listed in Table 10 after the DLT evaluation period will require a dose 
interruption and/or reduction.
Dose reductions may be considered for AEs occurring after the DLT evaluation period that do
not meet the criteria listed in Table 10 after discussion between the investigator and the sponsor.
Guidance for dose reduction is as follows:
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
Subjects requiring dose reductions for toxicities occurring on or BEFORE Cycle 1 
Day 28 (such as subjects who have experienced DLTs and recovered) should be 
reduced to the next lowest dose level that has been shown to be tolerated by at least 
3/3 or 5/6 subjects.

Subjects requiring dose reduction for toxicities occurring AFTER Cycle 1 Day 28
may be reduced to the next lowest dose level that has been shown to be tolerated by at 
least 3/3 or 5/6 subjects.
Table 9:
Example of Dose Reduction Steps
Current Dose
2.0 mg intermittent 5/7 
days
3.0 mg intermittent 5/7 
days
4.0 mg intermittent 5/7 
days
Dose reduction -1
1.0 mg intermittent 5/7 
days
2.0 mg intermittent 5/7 
days
3.0 mg intermittent 5/7 
days
Dose reduction -2
Discontinue
1.0 mg intermittent 5/7 
days
2.0 mg intermittent 5/7 
days
Dose reduction -3
-
Discontinue
Discontinue
8.2.9.2.
Intra-subject Escalation
Intra-subject dose escalation beyond the dose initially assigned to a subject is not permitted 
during the DLT evaluation period. Those continuing to take CC-122 longer term may, following 
approval by the SRC, have their dose level increased, provided that the alternative dose level has 
been shown to be well-tolerated in at least one cohort of other subjects in this study.
To be considered for intra-subject dose escalation, a subject must not have experienced ≥ Grade
3 toxicities at their assigned dose level.
8.2.9.3.
Treatment Delay
Treatment may be delayed up to 4 weeks until treatment-related toxicities (excluding alopecia) 
resolve to either ≤ Grade 1 or baseline levels. Treatment may restart either at the same, or a 
reduced dose level, at the investigator’s discretion or as described in Section 8.2.9.1.
During the DLT evaluation period, a treatment interruption that causes a subject to miss 3 doses
(need not be consecutive) for reasons other than DLTs will make a subject non-evaluable for 
DLTs and will necessitate the replacement of that subject in the dosing cohort.
8.2.9.4.
Dose Modification and Management of Toxicities
Guidelines for dose modification are listed below.
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Table 10:
Guidelines for Dose Modifications of CC-122 Related Toxicities
Toxicity
Modification
Hematologic toxicities
Grade 2 thrombocytopenia

No action
Grade 3 thrombocytopenia

Hold dosing until resolution to Grade ≤1 or baseline

Follow complete blood count (CBC) at least every 7 days

If resolution to Grade ≤1 or baseline occurs in ≤ 8 days, 
reintroduce CC-122 at the same dose level

If AE resolution occurs after > 8 days, or event reoccurs 
within the same cycle, reintroduce CC-122 at a lower dose 
level, if available
Grade 4 thrombocytopenia

Hold dosing until recovery to Grade ≤ 1 or baseline

Repeat CBC within 24 to 48 hours

Follow CBC at least every 7 days

Reintroduce CC-122 at a lower dose level, if available
Grade 3 neutropenia

Hold dosing until resolution to Grade ≤ 1

Follow CBC at least every 7 days

If AE resolution to Grade ≤ 1 occurs in ≤ 8 days, 
reintroduce CC-122 at the same dose level

If AE resolution occurs after > 8 days, or event reoccurs 
within the same cycle, reintroduce CC-122 at one dose 
level lower, if available
Grade 4 neutropenia

Hold dosing until recovery to Grade ≤ 1

Follow CBC at least every 5 days

Reintroduce CC-122 at a lower dose level, if available

Use of growth factors (granulocyte-colony stimulating 
factor [G-CSF], granulocyte macrophage-colony 
stimulating factor [GM-CSF]) is permitted at the discretion 
of the investigator
Febrile neutropenia

Hold further dosing until recovery to Grade ≤ 1 then 
resume dosing at one dose level lower, if available

Use of growth factors (G-CSF, GM-CSF) is permitted at 
the discretion of the investigator
Any hematological toxicity 
requiring interruption for > 4 
weeks

Discontinue CC-122
Non-hematologic toxicities
Any Grade 4 non-hematologic 
toxicity, including LFT elevations

Hold dosing until recovery to Grade ≤1 (or baseline LFT if 
liver tumors are present)

Reintroduce CC-122 at a lower dose level, if available
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Table 10:
Guidelines for Dose Modifications of CC-122 Related Toxicities (Continued)
Toxicity
Modification
Grade 3 or 4 clinical liver failure

Discontinue CC-122
Troponin-T > ULN with 
associated 20% increase in BNP 
over baseline with an absolute 
value > 100 pg/mL (confirmed on 
repeated measurements) without 
associated cardiac symptoms or 
findings

Hold dosing

Perform a cardiology evaluation, notify the sponsor

Follow troponin-T, BNP, and ECG at least every 7 days

If troponin-T returns to normal levels in ≤ 7 days and there 
are no other significant cardiac findings, restart CC-122 at 
the next lower dose level or the same dose

If troponin-T elevation persists beyond 7 days or recurs 
upon rechallenge, permanently discontinue CC-122
Troponin-T > ULN with cardiac 
symptoms or significant changes 
in ECG or LVEF

Permanently discontinue CC-122, notify the sponsor
Rash ≥ Grade 3

If Grade 3, hold dosing until recovery to Grade ≤ 1.

If AE resolution to Grade ≤ 1 occurs in ≤ 8 days, 
reintroduce CC-122 at the same dose level

If AE resolution to Grade ≤ 2 or resolution after > 8 days, 
reintroduce CC-122 at the next lower dose level, if 
available

Discontinue CC-122 for 2nd occurrence of ≥ Grade 3 rash

For desquamating (blistering) Grade 3 or any Grade 4 rash, 
discontinue CC-122

For maculopapular, acneiform, or pustular rashes lasting ≤ 
7 days medical management is warranted
Pneumonitis ≥ Grade 3

Discontinue CC-122
Grade 1 or 2 Tumor Flare 
Reaction (TFR)*
* assessed according to NCI 
CTCAE Version 3.0

Continue CC-122, maintain dose level

Nonsteroidal antiinflammatory drugs (NSAIDs) and/or 
narcotics may also be used as per the investigator’s 
discretion

Initiate therapy with corticosteroids as per the investigator’s 
discretion
Grade 3 or 4 TFR*

Hold CC-122 dosing

Initiate therapy with corticosteroids

NSAIDs and/or narcotics may also be used as per the 
investigator’s discretion

When symptoms resolve to < Grade 1, restart CC-122 at the 
same dose level
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Table 10:
Guidelines for Dose Modifications of CC-122 Related Toxicities (Continued)
Toxicity
Modification
Peripheral neuropathy
(neuropathies which begin or 
worsen while on study) ≥ Grade 3

Hold dosing at investigator’s discretion

When the toxicity resolves to ≤ Grade 2 or to baseline, 
restart CC-122 at the next lower dose level
Allergic reaction or 
hypersensitivity ≥ Grade 3

Discontinue CC-122
Venous thrombosis/embolism 
≥ Grade 3

Hold dosing and start anticoagulation therapy; restart CC-
122 at the investigator’s discretion (maintain dose level)
Other ≥ Grade 3 non-hematologic 
toxicity

Hold dosing at the investigator’s discretion

When the toxicity resolves to ≤ Grade 2, restart CC-122 at 
the same dose level or at the next lower dose level at the 
investigator´s discretion
Any non-hematologic toxicity 
requiring interruption for > 4 
weeks

Discontinue CC-122
Recurrence of Grade 3 non-
hematologic toxicity after dose 
reduction

Reduce dose to the next lower dose level, if available. If a 
lower dose is not available, discontinue CC-122
Recurrence of Grade 4 non-
hematologic toxicity after dose 
reduction

Discontinue CC-122
8.2.9.4.1. Dose Modification and Management of Cardiac Laboratory Abnormalities
In addition to routine ECG monitoring, additional monitoring for potential cardiac toxicity is 
included for subjects treated with CC-122. This includes routine monitoring of troponin-T and 
BNP, as well as monitoring of LVEF as described in Section 6. Elevations of troponin-T or BNP 
warrant further investigation, including assessment of the subject for signs and symptoms of 
cardiac injury, consideration of a cardiology consultation, other cardiac evaluations (such as an 
exercise stress test, additional evaluation of LVEF, or other cardiac tests recommended by a 
cardiologist), and the addition of cardioprotective therapy (for example, beta blockers), as 
appropriate. Laboratory evaluation to assess for assay interference may also be warranted.
Isolated asymptomatic elevations of troponin-T or BNP without associated ECG or LVEF 
changes or other cardiac findings do not require that dosing be held. For any elevation of 
troponin-T > ULN associated with either significant elevation of BNP (20% increase from 
baseline with an absolute value > 100 pg/mL) or associated cardiac symptoms or findings, CC-
122 dosing should be held and the sponsor should be notified. Additional cardiac monitoring 
should be performed as described in the table above and as medically indicated. CC-122 may be 
restarted, in consultation with the sponsor, based on troponin-T/BNP guidelines in Table 10 and 
general guidelines provided in Sections 8.2.9.1 and 8.2.9.3. For troponin-T elevations that either 
persist, recur with CC-122 rechallenge and/or are associated with cardiac symptoms or 
significant changes in ECG or LVEF, CC-122 should be permanently discontinued.
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8.2.9.4.2. Dose Modification and Management of Pneumonitis
Pneumonitis has been reported with CC-122. The diagnosis should be considered in subjects 
presenting with nonspecific respiratory signs and symptoms such as hypoxia, pleural effusion, 
cough, dyspnea, or interstitial pulmonary infiltrates, and in whom infectious, neoplastic and other 
causes are excluded by appropriate investigations. Subjects should be specifically advised to 
promptly report any new or worsening respiratory symptoms they experience. 
CC-122 dosing for those with radiological features suggestive of noninfectious pneumonitis but 
with minimal (Grade 1) symptoms may be interrupted per the investigator’s discretion. For drug-
related Grade 2 pneumonitis, CC-122 treatment should be interrupted and corticosteroids may be 
indicated. Once symptoms have resolved completely, CC-122 may be reintroduced at the next 
lower dose level. For drug-related Grade 3 or 4 pneumonitis, CC-122 must be permanently 
discontinued and corticosteroids used until clinical symptoms have resolved.
8.2.9.4.3. Dose Modification and Management of Tumor Flare Reaction
Subjects in this study should be monitored for tumor flare. 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, nonpruritic diffuse rash and in 
some cases increase in the peripheral blood lymphocyte counts. Tumor flare usually occurs 
within the first cycle of treatment. Tumor flare reaction may mimic progression of disease (PD); 
however, the TFR will generally subside over time. Therefore, careful monitoring and evaluation 
is important prior to discontinuing a study subject for PD in the initial cycles of CC-122 therapy.
There are currently no laboratory or radiological tests that distinguish TFR from PD. The 
distinction should be made on clinical grounds, incorporating observations such as associated 
physical findings, laboratory findings, and pace of disease before and after institution of 
treatment. Tumor flare will be recorded as an AE (graded using the NCI CTCAE 3.0 criteria) and 
not as PD.
Treatment of the TFR is up to the discretion of the investigator, depending on the severity and 
clinical situation. Recommendations for treatment are outlined in Table 10. Refer to Table 10 for 
further instructions and dose modifications for Grades 3 and 4 TFR. In mild to moderate cases, it 
is suggested that CC-122 be continued along with symptomatic treatment as outlined above. In 
more severe cases, CC-122 should be interrupted, as indicated in Table 10.
8.2.9.5.
Overdose
An overdose, as defined for this protocol, refers to CC-122 dosing only.
On a per dose basis, an overdose is defined as the following amount over the protocol-specified 
dose of CC-122 assigned to a given subject, regardless of any associated adverse events or 
sequelae.

PO any amount over the protocol-specified dose
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
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Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See Section 
11.1 for the reporting of adverse events associated with overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for CC-122 overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgment and 
experience of the treating physician.
8.3.
Method of Treatment Assignment
All subjects enrolled on this study will receive treatment with CC-122.
The investigators must explain the study to prospective patients, using the informed consent form 
and obtain the written consent from patients who wish to participate in the study prior to 
screening assessments. After the confirmation of the inclusion and exclusion criteria, the 
investigators will fax an enrollment form (if subject is eligible) to the registration center. After 
receiving confirmation from the registration center, dosing should be started within 7 days of 
receiving the confirmation of registration.
As this is a dose-escalation trial, the assignment of a subject to a particular dose level will be 
coordinated by the sponsor and the investigator.
8.4.
Packaging and Labeling
The label(s) for IP will include sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements, as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.5.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the investigator and relevant site personnel the process 
for Investigational Product return, disposal, and/or destruction including responsibilities for the 
site vs. Celgene (or designee).
The sponsor (or its designee) will deliver IP with the “Investigational Product Delivery Form” to 
the IP storage manager at the study site at the start of the study and thereafter as necessary. The 
IP storage manager will confirm the amount of IP received and submit the “Investigational 
Product Receipt Form” to the sponsor.
At the end of the study and when needed, the IP storage manager will return all of the unused IP, 
partially used IP, and empty bottles with the “Investigational Product Return Form” to the 
sponsor. The sponsor (or designee) will deliver the “Investigational Product Collection Form” to 
the IP storage manager. If any IP is missing or damaged, the sponsor should be notified 
immediately. The IP storage manager will document this in the “Investigational Product Return 
Form,” and the investigator will record this information in the source documents.
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8.6.
Investigational Product Compliance
The IP storage manager will manage the IPs following the instructions in the “Operating 
Procedure for Handling and Management of IPs” provided by the sponsor.
The IP storage manager will record receipt of IP from the sponsor, stock of IP at the study site, 
usage of IP by each subject, and return of unused drug to the sponsor or the disposition of IP. 
These records include the date, IP names/codes, quantity, lot numbers, and the subject number. 
The IP storage manager will also record whether the subject received IP at the dose specified in 
the protocol and whether IP supplied by the sponsor was appropriately managed and stored. 
Following completion of the study, the IP storage manager will sign and date these records 
verifying their accuracy. The IP storage manager will retain the original records, and copies of 
the records are to be submitted to the sponsor.
The investigator is responsible for accounting for all IPs that are issued to and returned by the 
subject during the course of the study. The investigators will instruct the subjects to manage IP 
by themselves, and return all unused drugs, if any due to missed doses or other reasons, 
including empty bottles to the study site.
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9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
In general, the use of any concomitant medication/therapies deemed necessary for the care of the
subject is permitted.
Prophylactic antiemetics will be withheld until the subject has experienced ≥ Grade 1 nausea or 
vomiting. The subject may then receive prophylactic antiemetics at the discretion of the treating 
physician.
Stable, therapeutic doses of anticoagulants are permitted. However, subjects on warfarin should
have PT/INR/PTT monitored according to Table 3 and as clinically indicated.
Subjects receiving recombinant erythropoietin or darbepoetin alfa for at least 4 weeks prior to
starting IP treatment may continue their pretreatment doses throughout the study. However, as of 
April 2015, note that recombinant erythropoietin and darbepoetin alfa are not approved for the 
treatment of cancer chemotherapy associated anemia in Japan.
G-CSF may be used to mitigate the duration of neutropenia in the following situations:

During Cycle 1: Grade 4 neutropenia lasting > 7 days or associated with fever (such 
as after experiencing a DLT of neutropenia)

After Cycle 1: ≥ Grade 3 neutropenia
Note: G-CSF should not be administered concurrently (within 24 hours) with CC-122.
Flu vaccination is permitted.
Routine infectious disease prophylaxis is not recommended. However, antibiotic, antiviral, 
antipneumocystis, antifungal, or other prophylaxis may be implemented during the study at the 
discretion of the investigator.
Pneumocystis pneumonia (PCP) prophylaxis may be initiated with two consecutive confirmed 
CD4 measurements < 200 / mm3.
Treatment with bisphosphonates (such as pamidronate, zolendronate), or other agents (such as
denosumab) to prevent or delay progression of bone metastases are permitted. Maintenance of a 
stable dosing regimen throughout the study is recommended.
Subjects may receive physiologic replacement doses of glucocorticoids (up to the equivalent of 
10 mg daily prednisone) as maintenance therapy for adrenal insufficiency.
Caution is recommended with the use of valproic acid due to the potential for drug interaction.
CC-122 absorbs ultraviolet (UV) light between the frequencies of 290 and 700 nm and has been 
shown to distribute to the skin and eyes in preclinical animal studies. As a precautionary measure, 
it is recommended that subjects avoid prolonged exposure to UV light, wear protective clothing 
and sunglasses, and use UV-blocking topical preparations while taking CC-122.
Subjects receiving CC-122 have developed venous thromboembolism/thromboembolism events 
reported as serious adverse events. Subjects and physicians are advised to be observant for the 
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signs and symptoms of thromboembolism. Subjects should be instructed to seek medical care if 
they develop symptoms, such as shortness of breath, chest pain, or arm or leg swelling. It is 
recommended that the investigator carefully assess an individual subject’s underlying risk for 
thromboembolism and bleeding and consider prophylactic measures with anticoagulation or 
antiplatelet agents.
9.2.
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is on the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than
the study treatments must not be given to subjects during the study. If such treatment is required,
the subject must be discontinued from the study.
However, focal palliative radiotherapy for treatment of cancer-related symptoms is allowed 
during study treatment at the discretion of the investigator.
9.3.
Required Concomitant Medications and Procedures
Every effort should be made to ensure that subjects are adequately hydrated prior to dosing.
Subjects who develop asymptomatic rises in TSH ≥10 mIU/L or symptomatic rises > 5 mIU/L
should receive supplementation with thyroxine according to local standard practice.
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10.
STATISTICAL ANALYSES
10.1.
Overview
The primary objectives of the study are to determine the safety and tolerability of CC-122, to 
define the MTD and/or RP2D, and to determine the plasma PK of CC-122 when administered 
orally to adult Japanese subjects with advanced solid tumors or NHL. The secondary objective of 
the study is to make a preliminary assessment of the antitumor activity of CC-122. The 
exploratory objectives of the study include evaluating the plasma PK of CC-122 formulated 
capsules and compare results to the plasma PK of CC-122 AIC, assessing the tolerability of 
CC-122 formulated capsules, 
 
In the following, statistical analyses will be performed by dose level, visit cycle and tumor type 
as needed or applicable.
10.2.
Study Population Definitions
The study population definitions are as follows:

Enrolled Population – includes all subjects enrolled, such as all subjects who are 
assigned an enrollment number.

Treated Population – all enrolled subjects who take at least one dose of CC-122.

Efficacy Population – all subjects who complete at least one cycle of their assigned
treatment regimen, and have a baseline and at least one post-baseline efficacy 
assessment.
10.3.
Sample Size and Power Considerations
A standard 3+3 design (Storer, 1989) will be used for dose escalation as described in Section 4.1, 
and approximately 15 subjects will be enrolled. Sample sizes are not based on statistical 
calculation but rather on clinical empirical and practical considerations traditionally used for 
phase 1 studies of this kind.
10.4.
Background and Demographic Characteristics
Subjects’ age, height, weight, and baseline characteristics will be summarized using descriptive 
statistics, while gender, race and other categorical variables will be provided using frequency 
tabulations. Medical history data will be summarized using frequency tabulations by system 
organ class and preferred term. The treated population will be used to summarize background 
and demographic characteristics.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both treatment 
and follow-up periods. A summary of subjects enrolled by site will be provided. Protocol 
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deviations will be summarized using frequency tabulations. The enrolled population will be used 
to summarize subject disposition.
10.6.
Efficacy Analysis
The efficacy population will be used for efficacy analysis. The efficacy variables of primary 
interest are tumor response. Tumor response (Appendix A, Section 19.1) will be based on 
investigator assessment using the Response Evaluation Criteria In Solid Tumors (RECIST) 
version 1.1 for solid tumors, and the International Workshop Group (IWG) Revised Criteria for 
Lymphoma. Subjects will be evaluated for tumor response on Day 15 of Cycle 2, 4, 6, and every 
3 cycles thereafter. A descriptive analysis of evidence of antitumor activity will be provided 
based on clinical, laboratory and radiographic assessments performed by the investigator, which 
includes assessments of target lesions, non-target lesions, new lesions and overall response. Both 
confirmed and unconfirmed responses by RECIST version 1.1 will be assessed.
The efficacy variable of focus will be best overall response. Duration of response will also be 
assessed. The data analyses of other preliminary efficacy variables will be detailed in the 
Statistical analysis plan (SAP).
10.7.
Safety Analysis
All subjects who receive at least one dose of study medication will be included in the safety
analyses. Adverse events, vital sign measurements, physical examination findings, clinical 
laboratory information, ECG interpretations, LVEF assessments and concomitant medications 
will be tabulated and summarized by dose level, visit cycle, and tumor type, as appropriate.
DLTs and all available safety information will be reviewed on an ongoing basis by the 
investigators and sponsor and summarized at the conclusion of each dose level. After completion 
of each dose cohort, the SRC will review the summarized data to determine the next step. 
Complete safety data for the DLT evaluation period will be summarized when all subjects have 
completed the DLT evaluation period.
Adverse events observed will be classified using the MedDRA classification system. The
severity of toxicities will be graded according to NCI CTCAE version 4.03 whenever possible.
The frequency of adverse events will be tabulated by MedDRA System Organ Class and
Preferred Term. In the by-subject analysis, a subject experiencing the same event more than once 
will only be counted once. Adverse events will be summarized by NCI CTCAE grade. Adverse 
events leading to discontinuation from treatment, events classified as Grade 3 or higher,
treatment-related events, serious adverse events, and deaths will be tabulated and listed
separately. Subject listings of all adverse events, serious adverse events, and their attributes will
be provided.
Clinical laboratory data will be summarized. Lab data will be graded according to NCI CTCAE 
version 4.03 whenever possible. The frequencies of the worst severity grade observed during 
treatment will be displayed in cross-tabulations by screening status.
Vital signs, ECG data and LVEF data will be summarized by cross-tabulations presenting normal
and abnormal values by number of subjects at pre- and post-IP initiation.
Graphical displays will be provided where useful in the interpretation of results.
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10.8.
Interim Analysis
No formal interim analysis is planned.
10.9.
Assessment of Pharmacokinetics
Pharmacokinetic measures are incorporated into the study to assess the extent of systemic
exposure, provided data is sufficient. Blood samples for PK will be collected at selected visits 
from all subjects. The following PK measurements will be determined for CC-122 after doses of 
CC-122 are given:

Area under the plasma concentration time-curve (AUC).

Peak (maximum) plasma concentration (Cmax).

Terminal half-life of (t1/2).

Time to maximum plasma concentration (Tmax).

Apparent clearance (CL/F).

Apparent volume of distribution (Vz/F).
Descriptive statistics (N, mean, standard deviation [SD], coefficient of variation [CV%], 
standard error [SE], geometric mean, geometric CV%, median, min, and max) will be provided 
for all data. Results will be presented in tabular and graphic forms as appropriate.
 
 
 
 
 
 
 
 
 
 
 
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event is any noxious, unintended, or untoward medical occurrence that may appear 
or worsen in a subject 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 subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (such as any clinically significant adverse change in the frequency or 
intensity of a preexisting condition) should be considered an AE.  A diagnosis or syndrome 
should be recorded on the AE page of the CRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose CRF. (See Section 8.2.9.5 for the definition of overdose.) Any sequela 
of an accidental or intentional overdose of an investigational product should be reported as an
AE on the AE CRF. If the sequela of an overdose is an SAE, then the sequelae must be reported 
on an SAE report form and on the AE CRF. The overdose resulting in the SAE should be 
identified as the cause of the event on the SAE report form and CRF but should not be reported 
as an SAE itself.
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 findings from 
other tests and/or procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent 
until 28 days after the last dose of IP and those SAEs made known to the investigator at any time 
thereafter that are suspected of being related to IP. AEs and serious adverse events will be 
recorded on the AE page of the CRF and in the subject’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.  
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
An SAE is any AE occurring at any dose that:

Results in death;

Is life-threatening (in the opinion of the investigator, the subject is at immediate risk 
of death from the AE);
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
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);

Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’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 subject 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 for:

A standard procedure for protocol therapy administration.  However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE.

Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.

The administration of blood or platelet transfusion as routine treatment of studied 
indication.  However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.

A procedure for protocol/disease-related investigations (such as surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling).  However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.

Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.

A procedure that is planned (planned prior to starting of treatment on study); must be 
documented in the source document and the CRF.  Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.

An elective treatment of or an elective procedure for a preexisting condition unrelated 
to the studied indication.

Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the CRF and the SAE Report Form 
must be completed.
For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
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11.2.2.
Severity/Intensity
For both AEs and SAEs, the investigator must assess the severity/intensity of the event.
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of CTCAE version 4.03.
http://www.jcog.jp/doctor/tool/CTCAEv4J_20111217.pdf
AEs that are not defined in the CTCAE should be evaluated for severity/intensity according to 
the following scale:

Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required

Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required

Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible

Grade 4 = Life-threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable

Grade 5 = Death - the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious,” which is 
based on subject/event outcome or action criteria associated with events that pose a threat to a 
subject’s life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means a causal relationship of the adverse event to IP 
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the IP 
and the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
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If an event is assessed as suspected of being related to a comparator, ancillary or additional IP
that has not been manufactured or provided by Celgene, please provide the name of the
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(for example, discontinuation, interruption, or reduction of IP, as appropriate) and report if 
concomitant and/or additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs.
All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until these events have recovered, recovered with sequelae, not recovered or 
have resulted in death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:

results in discontinuation from the study;

requires treatment, modification/interruption of IP dose, or any other therapeutic 
intervention; or

is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.  
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/screen 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. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (for example, record thrombocytopenia rather than decreased 
platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 28 days of the 
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subject’s last dose of IP, are considered immediately reportable events.  IP is to be discontinued 
immediately and the subject instructed to return any unused portion of the IP to the investigator.  
The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Celgene 
Drug Safety immediately by facsimile, or other appropriate method, using the Pregnancy Initial 
Report Form, or approved equivalent form.
The exposure of any pregnant female (for example, caregiver or pharmacist) to CC-122 is also an 
immediately reportable event.
The female subject should be referred to an obstetrician-gynecologist, preferably one 
experienced in reproductive toxicity for further evaluation and counseling. Female subjects must 
avoid breastfeeding for at least 28 days after the last dose of CC-122.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (for example, spontaneous abortion), the 
investigator should report the abnormal outcome as an AE.  If the abnormal outcome meets any 
of the serious criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or 
other appropriate method, within 24 hours of the investigator’s knowledge of the event using the 
SAE Report Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs.  In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject taking investigational product becomes pregnant, the male 
subject taking IP should notify the investigator, and the pregnant female partner should be 
advised to call their healthcare provider immediately.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the CRF.  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.  This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms is accurate and consistent.  
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent until 28 days after the last dose of IP) or any 
SAE made known to the investigator at any time thereafter that are suspected of being related to 
IP.  SAEs occurring prior to treatment (after signing the ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents.  If a subject died and an autopsy has been 
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performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available.  Any follow-up data should be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.  
Where required by local legislation, the investigator is responsible for informing the Head of the 
Institution and the institutional review board (IRB) of the SAE and providing them with all 
relevant initial and follow-up information about the event. The investigator must keep copies of 
all SAE information on file including correspondence with Celgene and the IRB.
11.5.1.
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 (for example, missing causality assessment) may be handled by phone.
11.6.
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 CC-122 based on the Investigator Brochure.
Celgene or its authorized representative shall notify the investigators and the Heads of the 
Institutions of the following information

Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (Suspected Unexpected Serious Adverse 
Reactions [SUSARs]);

Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.

In Japan, measures taken in foreign countries to ensure patient safety, study reports 
that indicates potential risk of cancer, etc., or biannual SAE report according to the 
local regulations.
Where required by local legislation, the investigator shall notify his/her IRB and the Head of the 
Institution promptly of these new serious and unexpected AE(s) or significant risks to subjects.
The investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB.  (See Section 15.3 for record retention information.)
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form Completion Guidelines or to the Pregnancy Report Form Completion Guidelines.
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12.
DISCONTINUATIONS
The following events are considered sufficient reasons for discontinuing a subject from the 
investigational product and/or from the study:

Adverse Event

Disease progression

Withdrawal by subject

Death

Lost to follow-up

Protocol violation

Physician decision
The reason for discontinuation should be recorded in the CRF and in the source documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which 
will not be delayed or refused by the sponsor.  However, prior to discontinuing a subject, the 
investigator may contact the sponsor and forward appropriate supporting documents for review 
and discussion.
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13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on-call Celgene/Contract 
research organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24 hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study. Therefore, IP will be identified on the package labeling.
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14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations.  Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an informed consent 
document and are screened for entry into the study.  Subjects who fail screening must have the 
reason(s) recorded in the subject’s source documents and the CRF.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (such 
as medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The investigator must ensure timely and accurate completion of CRF and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures.
Documentation that informed consent occurred prior to the study subject’s entry into the study 
and of the informed consent process should be recorded in the study subject’s source documents,
including the date.  The original informed consent document signed and dated by the study 
subject and by the person consenting the study subject prior to the study subject’s entry into the 
study must be maintained in the investigator’s study files and a copy given to the study subject.  
In addition, if a protocol is amended and it impacts on the content of the informed consent, the 
informed consent document must be revised.  Study subjects participating in the study when the 
amended protocol is implemented must be reconsented with the revised version of the informed 
consent document.  The revised informed consent document signed and dated by the study 
subject and by the person consenting for the study subject must be maintained in the 
investigator’s study files and a copy given to the study subject.
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14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
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 
subject’s signed informed consent document, it is the responsibility of the investigator to obtain 
such permission in writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor.  Amendments will be submitted to the IRB for written approval.  
Written approval must be obtained before implementation of the amended version occurs.  The 
written signed approval from the IRB should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB approval but will be submitted to the IRB for 
information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, informed consent document, and any other 
appropriate documents will be submitted to the IRB with a cover letter or a form listing the 
documents submitted, their dates of issue, and the site (or region or area of jurisdiction, as 
applicable) for which approval is sought. If applicable, the documents will also be submitted to 
the authorities in accordance with local legal requirements.
IP can only be supplied to an investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB and their occupation and qualifications. If the IRB will not disclose the 
names, occupations and qualifications of the committee members, it should be asked to issue a 
statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB should mention the protocol title, number, amendment number (if 
applicable), study site (or region or area of jurisdiction, as applicable), and any other documents 
reviewed. It must mention the date on which the decision was made and must be officially signed 
by a committee member. Before the first subject is enrolled in the study, all ethical and legal 
requirements must be met.
The IRB and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the informed consent document 
should also be revised.
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The investigator must keep a record of all communication with the IRB and, if applicable, 
between a Coordinating investigator and the IRB. This statement also applies to any 
communication between the investigator (or Coordinating investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB prior to use.
14.7.
Ongoing Information for Institutional Review Board/Ethics 
Committee
If required by legislation or the IRB, the investigator must submit to the IRB:

Information on serious or unexpected adverse events as soon as possible; 

Periodic reports on the progress of the study;

Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (for example, for the IRB, regulatory authorities, etc.).
In addition, the investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:

Unsatisfactory enrollment;

GCP noncompliance;

Inaccurate or incomplete data collection;

Falsification of records;

Failure to adhere to the study protocol.
14.9.
Compensation for Injured Subjects
Celgene is prepared to compensate for the costs of medical care and others losses associated with 
study-related injuries.
The compensation for injured subjects and the payment to them will be specified in the informed 
consent document.
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15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the investigational product are complete, accurate, filed and 
retained.  Examples of source documents include: hospital records; clinic and office charts; 
laboratory notes; memoranda; subject’s diaries or evaluation checklists; dispensing records; 
recorded data from automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiche; x-ray film and reports; and records kept at the pharmacy, and
the laboratories, as well as copies of the CRFs or compact disc read-only memory (CD-ROM).
15.2.
Data Management
Data will be collected via electronic CRFs/an electronic data capture (EDC) system. 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 
electronic CRFs/EDC system.  An audit trail within the system will track all changes made to the 
data.
15.3.
Record Retention
Essential documents must be retained by the Head of the Institution and investigator for a 
minimum of the time period listed below or according to local laws or requirements, whichever 
is longer:

Two 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

At least two years have elapsed since the formal discontinuation of clinical 
development of the IP

Until the marketing application of the IP is approved in Japan

Three years have elapsed since the formal completion (discontinuation) of the clinical 
trial in Japan
Essential documents include, but are not limited to, the following:

Signed informed consent documents for all subjects;

Subject identification code list, screening log (if applicable), and enrollment log;

Record of all communications between the investigator, the Head of the Institution
and the IRB;

Composition of the IRB;

Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
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
List of sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;

Copies of CRFs (if paper) and of documentation of corrections for all subjects;

IP accountability records;

Record of any body fluids or tissue samples retained;

All other source documents (subject records, hospital records, laboratory records, 
etc.); 

All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Head of the Institution and the investigator must notify Celgene if they wish to assign the 
essential documents to someone else, remove them to another location or is unable to retain them 
for a specified period.  The Head of the Institution and the investigator must obtain approval in 
writing from Celgene prior to destruction of any records. If the Head of the Institution and the 
investigator are unable to meet this obligation, they must ask Celgene for permission to make 
alternative arrangements. Details of these arrangements should be documented.
All study documents should be made available if required by relevant health authorities. The 
Head of the Institution and the investigator/institution should take measures to prevent accidental 
or premature destruction of these documents.
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16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study.  All aspects of the study are reviewed with the investigator and the staff at a study 
initiation visit and/or at an investigator meeting.  Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, CRFs, 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.  During monitoring visits, the facilities, 
investigational product storage area, CRFs, subject’s source documents, and all other study 
documentation will be inspected/reviewed by the Celgene representative in accordance with the 
Study Monitoring Plan.
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.  Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The Head of the Institution and the investigator are required to permit direct access to the 
facilities where the study took place, source documents, CRFs and applicable supporting records 
of study subject participation for audits and inspections by IRBs, regulatory authorities (for 
example, Food & Drug Administration [FDA], European Medicines Agency [EMA], Health 
Canada) and company authorized representatives.  The Head of the Institution and the 
investigator should make every effort to be available for the audits and/or inspections.  If the 
Head of the Institution or the investigator is contacted by any regulatory authority regarding an 
inspection, he/she should contact Celgene immediately.
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17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes.  Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations.  Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.
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CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
18.
REFERENCES
Cheson BD, Pfistner B, Juweid, ME, et al. Revised Response Criteria for Malignant Lymphoma. 
J Clin Oncol 2007; 25: 579-586.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1). European J Cancer 2009; (45) 228–247.
Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J 
Med. 2008; 359(22): 2313-23.
Storer B. Design and Analysis of Phase I Clinical Trials. Biometrics 1989; 45: 925-937.
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19.
APPENDICES
19.1.
Appendix A
19.1.1.
Guidelines for Tumor Response Evaluation
19.1.1.1.
Solid Tumors
The Guidelines for the New Response Evaluation Criteria in Solid Tumors (RECIST, 
[Eisenhauer, 2009]) can be accessed online at:
www.eortc.be/recist/documents/RECISTGuidelines.pdf
19.1.1.2.
Lymphoma
The International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 
2007) can be accessed online at the following address:
http://jco.ascopubs.org/cgi/reprint/25/5/579
(click on “manual download for full text PDF of manuscript)
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19.2.
Appendix B
19.2.1.
CC-122 Pregnancy Prevention Risk Management Plan
Specific details regarding the CC-122 Pregnancy Prevention Risk Management Plan will be 
provided via a separate, stand-alone document.
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EDMS Doc. Number: 21574111 - 19880032
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.
UserName: 
Title:  
Date: 
Meaning: Approved, no changes necessary.
 ================================================
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EDMS Doc. Number: 21574111 - 20211995
CC-122
Summary of Changes CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
3
CC-122-ST-002 Amendment No. 03 Final: 13 Dec 2016
1.
JUSTIFICATION FOR AMENDMENT
The primary purpose of protocol amendment 03 is to adjust the visit schedule for Cycle 5 
onwards and to clarify that dose escalation will stop if the MTD in global CC-122 studies in 
various indications is reached.
Given that safety has been confirmed in the 2, 3, and 4 mg active ingredient in capsule (AIC) 
dose levels (dose levels 1-3) as documented in the Safety Review Committee (SRC) dose-
escalation meeting minutes and given that several patients have remained on study for as long as 
12 cycles with no major safety issues, the visit schedule from Cycle 5 onwards is being changed 
to allow for less frequent study visits to ease the burden on patients having to visit the study site 
for study assessments.
The clarification regarding stopping dose escalation if the MTD in global studies in various 
indications is reached was added to allow flexible decision-making based on other ongoing 
studies being conducted globally and not just the CC-122-ST-001 study.
The changes to the protocol are as follows:
!
The study design section of the protocol summary was updated to include language 
regarding stopping dose escalation if the MTD in global CC-122 studies in various 
indications is reached.
!
Section 4.1.1 was also revised to include the revised wording stated in the bullet above.
!
The table of events (Table 3) in Section 5 has been updated to allow for once monthly 
visits from Cycle 5 onwards (with the exception of Cycles with tumor assessments, e.g. 
Cycle 6 and every 3 cycles thereafter, wherein a Day 15 visit is necessary) instead of 
weekly visits.
!
A footnote under the table of events was updated to more accurately reflect the pregnancy 
prevention risk management plan.
!
Section 8.2.8 was also revised to include the revised wording regarding stopping dose 
escalation if the MTD in global CC-122 studies in various indications is reached.
The amendment also includes a few minor formatting and editing changes for added clarity.
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CC-122
Summary of Changes CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
3
CC-122-ST-002 Amendment No. 02 Final: 28 Mar 2016
1.
JUSTIFICATION FOR AMENDMENT
The primary purpose of protocol amendment 02 is to introduce the evaluation of a formulated 
capsule of CC-122.
The current active ingredient in capsule (AIC) and the new CC-122 formulated capsules were 
evaluated in healthy adult subjects in a separate study (CC-122-CP-002 Part 2, which is 
clinically completed). The CC-122 formulated capsules have different CC-122 free base (the 
active moiety) amounts compared with CC-122 AIC capsules that were employed from the 
beginning of the current study. CC-122 AIC 0.5, 1, and 3 mg strengths were based on CC-122 
HCl (the salt form) and are equivalent to 0.44, 0.88, and 2.64 mg CC-122 free base, respectively. 
CC-122 formulated capsules of 1, 3, 3.5 and 4 mg strengths are based on CC-122 free base and 
are equivalent to 1.13, 3.38, 3.95 and 4.51 mg CC-122 HCl, respectively.
Following a single oral administration of CC-122 at the dose level of 3 mg, the drug exposure 
(AUCinf and Cmax) was higher in subjects administered CC-122 formulated capsules than in 
subjects administered CC-122 AIC (16.29% and 35.58%, respectively). Given the increased 
exposure in healthy adults, pharmacokinetic (PK) and safety evaluations of the CC-122 
formulated capsules will be performed in subjects with cancer within the current CC-122-ST-002
study.
The changes to the protocol are as follows:
!
the addition of updated information from ongoing studies in Section 1.1.3
!
the addition of exploratory objectives and endpoints to assess the PK and tolerability of 
the formulated capsules to the Protocol Summary and Sections 2 and 3
!
 
 
!
the addition of a provisional dose cohort using formulated capsules to the Protocol 
Summary and Section 4
!
the addition of information on previous clinical experience with the formulated capsules 
to Section 1
!
 
 
!
the revision of the expected number of subjects from 12 to 15 in the Protocol Summary 
and Sections 7 and 10 in line with the addition of a provisional cohort
!
the addition of information on the formulated capsules to Section 8
!
 
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CC-122
Summary of Changes CC-122-ST-002
Celgene K.K.
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CC-122-ST-002 Amendment No. 02 Final: 28 Mar 2016
The amendment also includes a change in the responsible medical monitor, as well as a few 
minor language and formatting changes for added clarity.
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EDMS Doc. Number: 20221436 - 20211995
CC-122
Protocol CC-122-ST-002
Celgene K.K.
Confidential and Proprietary
3
CC-122-ST-002 Amendment No. 01 Final: 09 Apr 2015
1.
JUSTIFICATION FOR AMENDMENT
The primary purpose of this protocol amendment is to include the following changes 
 
!
changing the duration of recommendation for hospitalization during Cycle 1 from 2 
weeks to the entire DLT evaluation period (Cycle 1) in Section 5
!
the addition of language stating that contraception methods should be approved or 
certified in Japan in Section 6.2.5
!
the addition of thrombocytopenia requiring platelet transfusions as a dose-limiting 
toxicity in Section 8.2.6
!
the addition of language stating that recombinant erythropoietin and darbepoetin alfa are 
not approved for the treatment of cancer chemotherapy associated anemia in Japan in 
Section 9.1
!
the addition of language stating that female subjects must avoid breastfeeding for at least 
28 days after the last dose of CC-122 to Section 11.4.1
 
 
The amendment also includes a change in the responsible medical monitor, as well as the 
deletion of a sentence in Section 14.9 as a result of changes to the Japanese protocol template 
language and minor formatting changes.
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