Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 (Mogamulizumab) Versus Vorinostat in Subjects With Previously Treated Cutaneous T-Cell Lymphoma
Phase: PHASE3
Conditions: Cutaneous T-Cell Lymphoma
Sponsor: Kyowa Kirin, Inc.

 
CONFIDENTIAL 
1 
PROTOCOL 0761-010 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell 
Lymphoma 
REVISED TO INCORPORATE AMENDMENT 10 
Protocol Number: 
0761-010 
Replaces 
Amendment 9: 
 
20 Apr 2018 
Amendment 10: 
31 May 2018 
Phase: 
3 
IND Number: 
101,843 
EudraCT Number: 
2012-004766-17 
Sponsor: 
Kyowa Kirin Pharmaceutical Development, Inc. 
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
+1 609 919-1100 
 
Study Monitors: 
 
 
  
 
 
 
 
  
Medical Monitors: 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
The information contained in this document is the property of or under the control of Kyowa Kirin Pharmaceutical 
Development, Inc. and its affiliated companies. This information is provided to you in confidence as an investigator, 
potential investigator or consultant, for review by you, your staff and applicable Institutional Review Board/Ethics 
Committee. You shall not disclose this information to others without prior written authorization from Kyowa Kirin 
Pharmaceutical Development, Inc., except to the extent necessary to obtain informed consent from those persons to whom 
the drug may be administered, and except as may be required by federal, state, or local laws or regulations. 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
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Principal Investigator Signature Page 
Protocol Title:  Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal 
Antibody KW-0761 (mogamulizumab) Versus Vorinostat in Subjects with Previously 
Treated Cutaneous T-Cell Lymphoma 
 
Protocol Number:  0761-010, Amendment 10 
 
CONFIDENTIALITY STATEMENT 
This protocol contains information that is proprietary to Kyowa Kirin Pharmaceutical 
Development, Inc. (KKD). This information is being provided to you for the purpose of 
conducting a clinical trial on behalf of KKD. You may disclose the contents of this protocol 
to the study personnel under your supervision and to your Institutional Review Board (IRB) 
or Ethics Committee (EC). As a Clinical Investigator participating in this study you agree to 
not disclose the contents of this protocol to any other parties (unless such disclosure is 
required by government regulations or laws) without the prior written permission of KKD. 
Any supplemental information (e.g., protocol amendment, Investigator’s Brochure) that may 
accompany this document is also proprietary to KKD and should be handled consistent with 
the terms stated above. 
By my signature below, the Principal Investigator attests that they have read, understood, and 
agree to abide by all conditions, instructions, and restrictions contained in this protocol 
(including appendices). The Principal Investigator will not initiate this study without approval 
from the appropriate IRB or Ethics Committee and understands that any changes in the 
protocol must be approved in writing by the Sponsor and the IRB or Ethics Committee before 
they can be implemented, except where necessary to eliminate immediate hazards to the 
subject. 
 
Principal Investigator: 
 
______________________________________________    ________________________ 
Printed Name/Signature 
 
 
 
 
Date 
________________________________________________________________________ 
Institution 
________________________________________________________________________ 
Address 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Protocol Signature Page  
Protocol Title:  Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal 
Antibody KW-0761 (mogamulizumab) Versus Vorinostat in Subjects with Previously 
Treated Cutaneous T-Cell Lymphoma 
 
Protocol Number:  0761-010, Amendment 10 
 
 
 
 
Signature 
 
 
  
 
 
Date 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
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Summary of Changes in Amendment 10 
A new section (Section 7.8) was added to the protocol to specify procedures to be followed 
for subjects who are ongoing in the study at the time of initial marketing authorization.  
These procedures should be implemented upon notification by the Sponsor. 
1) For subjects who are continuing to receive KW-0761, the Sponsor will continue to 
supply study drug until KW-0761 becomes commercially available (reimbursable) in 
the country/region of the study site or until KW-0761 is not approved for marketing 
for the indication and regimen under study in the country/region of the study site. 
2) For all ongoing subjects, i.e., subjects who are continuing to receive KW-0761 or who 
are in safety or survival follow-up at the time of initial marketing authorization, 
changes in study procedures and data collection are described. 
References to Section 7.8 were added as relevant in other protocol sections. 
Other minor updates were made for consistency. 
The Sponsor does not consider that these changes impact the overall risk/benefit of this study. 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Serious Adverse Event Contact Information 
US, Europe, Australia 
Japan 
Drug Safety Surveillance 
Phone: +1-609-919-1100 
Available 9:00 am-5:00 pm (Eastern time) 
2:00 pm-10:00 pm (GMT) 
US SAE Fax: +1-800-209-2251 
UK SAE Fax:  +44 808 171 9999 
e-mail address:  saesource@kyowakirin.com 
Available 24 hours daily 
 
Drug Safety Surveillance 
SAE Fax: +81-3-6683-7721 
 
 
After hours Contacts: 
All US, EU, Australian Study Sites: 
Dmitri O. Grebennik, MD 
Medical Monitor-KKD 
Phone: +1-609-902-4703 
dmitri.grebennik@kyowakirin.com 
 
Japanese Study Sites: 
Yoshihiro Hara, MD, PhD 
CMIC Co., Ltd. 
Tel：+81-80-3341-3861 
Fax：+81-3-6683-7721 
yoshihiro-hara.kh@cmic.co.jp 
 
 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Table of Contents 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE ...................................................... 2 
PROTOCOL SIGNATURE PAGE ..................................................................................... 3 
SUMMARY OF CHANGES IN AMENDMENT 10 .......................................................... 4 
SERIOUS ADVERSE EVENT CONTACT INFORMATION .......................................... 5 
TABLE OF CONTENTS ..................................................................................................... 6 
LIST OF IN-TEXT TABLES ............................................................................................ 11 
LIST OF APPENDICES.................................................................................................... 11 
PROTOCOL SYNOPSIS .................................................................................................. 12 
LIST OF ABBREVIATIONS ............................................................................................ 27 
1 
BACKGROUND AND RATIONALE .................................................................... 30 
1.1 
Cutaneous T-Cell Lymphomas ............................................................................... 30 
1.2 
Treatment of Cutaneous T-cell Lymphomas ........................................................... 31 
1.3 
Chemokine Receptor 4 and T-Cell Malignancies .................................................... 31 
1.4 
KW-0761 (mogamulizumab) .................................................................................. 33 
1.5 
Safety and Efficacy of KW-0761 ............................................................................ 33 
1.6 
Vorinostat (ZOLINZA®) ........................................................................................ 34 
1.7 
Rationale ................................................................................................................ 36 
2 
OBJECTIVES .......................................................................................................... 37 
2.1 
Primary Objectives ................................................................................................. 37 
2.2 
Secondary Objectives ............................................................................................. 37 
2.3 
Exploratory Objectives ........................................................................................... 38 
3 
STUDY POPULATION .......................................................................................... 38 
3.1 
Subject Selection .................................................................................................... 38 
3.2 
Inclusion Criteria .................................................................................................... 38 
3.3 
Exclusion Criteria ................................................................................................... 40 
3.4 
Eligibility for Cross-over to KW-0761 .................................................................... 41 
4 
INVESTIGATIONAL PLAN .................................................................................. 42 
4.1 
Overview of Study Design ...................................................................................... 42 
4.2 
Number of Subjects ................................................................................................ 42 
4.3 
Investigational Centers ........................................................................................... 42 

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5 
TREATMENT PLAN .............................................................................................. 42 
5.1 
Assignment to Study............................................................................................... 42 
5.2 
Study Treatments.................................................................................................... 42 
5.2.1 
Study Drug: KW-0761 (mogamulizumab) ........................................................... 43 
5.2.1.1 
Premedication Prior to KW-0761 Infusion ....................................................... 43 
5.2.1.2 
Definition of Treatment Cycle ......................................................................... 43 
5.2.1.3 
Delays in Dosing ............................................................................................. 43 
5.2.1.4 
Duration of Treatment ..................................................................................... 43 
5.2.1.5 
Replacement of Subjects .................................................................................. 44 
5.2.1.6 
Dose Modifications .......................................................................................... 44 
5.2.1.7 
Treatment of Hypersensitivity-Like Reactions ................................................. 44 
5.2.1.8 
Treatment Emergent Skin Rash ........................................................................ 46 
5.2.2 
Study Drug: Vorinostat (ZOLINZA®) ................................................................. 48 
5.2.2.1 
Definition of Treatment Cycle ......................................................................... 49 
5.2.2.2 
Delays in Dosing ............................................................................................. 49 
5.2.2.3 
Duration of Treatment ..................................................................................... 49 
5.2.2.4 
Replacement of Subjects .................................................................................. 50 
5.2.2.5 
Dose Modifications .......................................................................................... 50 
5.3 
Cross-over to Study Drug KW-0761 ....................................................................... 50 
5.4 
Concomitant Therapy ............................................................................................. 51 
5.4.1 
Permitted Treatment ............................................................................................ 51 
5.4.2 
Prohibited Treatment........................................................................................... 52 
5.5 
Criteria for Removal from Study ............................................................................ 53 
6 
STUDY PROCEDURES.......................................................................................... 54 
7 
STUDY MEASUREMENTS ................................................................................... 54 
7.1 
Safety Evaluations .................................................................................................. 55 
7.1.1 
Clinical Laboratory Evaluations .......................................................................... 55 
7.1.2 
Vital Signs and Body Weight .............................................................................. 57 
7.1.3 
Physical Examination .......................................................................................... 58 
7.1.4 
Electrocardiograms ............................................................................................. 58 
7.1.5 
Blood Sample for Determination of Natural Ligands ........................................... 58 

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7.1.6 
Genomic Sampling (For subjects receiving KW-0761 as first assigned 
therapy only) ....................................................................................................... 59 
7.1.7 
Immunogenicity (For subjects receiving KW-0761) ............................................ 59 
7.2 
Efficacy Evaluations ............................................................................................... 59 
7.2.1 
Evaluation of Skin Disease.................................................................................. 60 
7.2.1.1 
Skin Biopsy ..................................................................................................... 60 
7.2.1.2 
Skin Photographs ............................................................................................. 61 
7.2.1.3 
Modified Severity Weighted Assessment Tool (mSWAT) ............................... 62 
7.2.1.4 
Response Criteria for Skin ............................................................................... 63 
7.2.1.5 
Pruritus Evaluation .......................................................................................... 64 
7.2.2 
Evaluation of Blood Disease ............................................................................... 64 
7.2.2.1 
Flow Cytometric Analysis ............................................................................... 64 
7.2.2.2 
Response Criteria in Blood .............................................................................. 65 
7.2.3 
Evaluation of Disease in Lymph Nodes and Viscera............................................ 65 
7.2.3.1 
Baseline Tumor Assessments ........................................................................... 65 
7.2.3.2 
Method of Tumor Response Assessment .......................................................... 65 
7.2.3.3 
Determination of Response in Lymph Nodes and Viscera ................................ 66 
7.2.4 
Global Composite Response Score ...................................................................... 68 
7.2.4.1 
Independent Review of Progression ................................................................. 69 
7.3 
Pharmacokinetics (for subjects receiving KW-0761) .............................................. 70 
7.4 
Quality of Life Assessments ................................................................................... 70 
7.5 
Follow-Up .............................................................................................................. 70 
7.6 
Follow-Up for Subjects Achieving a Complete Response ....................................... 71 
7.7 
Study Procedures for Subjects Continuing Study Treatment at the Time 
of Primary Efficacy Analysis .................................................................................. 72 
7.8 
Study Procedures for Subjects Ongoing at the Time of Regional Drug 
Approval ................................................................................................................ 73 
8 
STUDY AGENTS .................................................................................................... 74 
8.1 
KW-0761 (mogamulizumab) .................................................................................. 74 
8.1.1 
Description ......................................................................................................... 74 
8.1.2 
Preparation of Dose............................................................................................. 74 
8.1.3 
Study Drug Administration ................................................................................. 74 

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8.1.4 
KW-0761 Formulation and Storage ..................................................................... 75 
8.1.5 
Packaging and Labeling of KW-0761 .................................................................. 75 
8.1.5.1 
Labeling .......................................................................................................... 76 
8.1.6 
Drug Accountability ............................................................................................ 76 
8.1.7 
Return and Destruction ....................................................................................... 76 
8.2 
Vorinostat (ZOLINZA®) Capsules.......................................................................... 76 
8.2.1 
Description ......................................................................................................... 76 
8.2.2 
Administration .................................................................................................... 77 
8.2.3 
Vorinostat Adverse Events .................................................................................. 77 
8.2.4 
Return and Destruction ....................................................................................... 77 
9 
ADVERSE EVENT REPORTING IN CLINICAL TRIALS ................................ 77 
9.1 
Definitions ............................................................................................................. 78 
9.1.1 
Adverse Events ................................................................................................... 78 
9.1.2 
Adverse Event Severity ....................................................................................... 79 
9.1.3 
Adverse Event Relationship to Study Drug ......................................................... 79 
9.2 
Serious Adverse Events .......................................................................................... 80 
9.3 
Other Safety Considerations ................................................................................... 82 
9.4 
Adverse Event Contacts .......................................................................................... 82 
9.5 
Data Safety Monitoring Board ................................................................................ 82 
10 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS........................... 82 
10.1 
Populations to be Analyzed .................................................................................... 83 
10.2 
Analyses of Safety Data.......................................................................................... 83 
10.3 
Analyses of Efficacy Data ...................................................................................... 84 
10.4 
Exposure-Response Analysis .................................................................................. 88 
11 
ETHICAL ASPECTS .............................................................................................. 88 
11.1 
Ethics and Good Clinical Practice ........................................................................... 88 
11.2 
Ethics Committee/Institutional Review Board ........................................................ 89 
11.3 
Informed Consent ................................................................................................... 89 
12 
INVESTIGATOR OBLIGATIONS AND STUDY MANAGEMENT .................. 91 
12.1 
Administrative ........................................................................................................ 91 
12.2 
Changes in Protocol ................................................................................................ 91 

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12.3 
Protocol Deviations ................................................................................................ 91 
12.4 
Monitoring and Quality Assurance ......................................................................... 91 
12.5 
Electronic Case Report Forms (eCRFs) and Source Documentation ....................... 92 
12.6 
Record Retention .................................................................................................... 93 
12.7 
Confidentiality ....................................................................................................... 93 
12.8 
Disclosure .............................................................................................................. 94 
12.9 
Termination of Study .............................................................................................. 94 
12.10 
Final Report/Publications ....................................................................................... 94 
13 
REFERENCES ........................................................................................................ 96 
14 
APPENDICES ....................................................................................................... 101 
 
 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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List of In-text Tables 
Table 1 
Study Procedures:  First Treatment Cycle ....................................20 
Table 2 
Study Procedures:  Subsequent Cycles in Year 1 .........................22 
Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda ....24 
Table 5.2.1-1 
Guidelines for Treatment of Skin Rash ........................................48 
Table 7.1.1-1 
Clinical Laboratory Assessments .................................................57 
Table 7.2.1-1 
Modified Severity Weighted Assessment Tool ............................62 
Table 7.2.1-2 
Modified Severity Weighted Assessment Tool Score ..................63 
Table 7.2.1-3 
Response Criteria for Skin, as assessed by mSWAT scoresa ........64 
Table 7.2.2-1 
Blood Response Criteriaa .............................................................65 
Table 7.2.3-1 
Response in Lymph Nodesa .........................................................67 
Table 7.2.3-2 
Response in Viscera ....................................................................68 
Table 7.2.4-1 
Global Composite Scoring System ..............................................69 
Table 10.3-1 
Required PFS Events and Power for Comparison of PFS Kaplan-
Maier Curves Between the Vorinostat and KW-0761 Arms at the 
0.025 Level .................................................................................88 
 
List of Appendices 
Appendix 1 
Modified ISCL/EORTC Revisions to the TNMB Classification 
of MF/SS .................................................................................. 102 
Appendix 2 
Eastern Cooperative Oncology Group (ECOG) Scale ................ 103 
Appendix 3 
NYHA Classification ................................................................ 104 
Appendix 4 
Autoimmune Screening Questionnaire ...................................... 105 
Appendix 5 
Itchy Quality of Life Questionnaire ........................................... 106 
Appendix 6 
Skindex-29 ................................................................................ 107 
Appendix 7 
FACT-G .................................................................................... 108 
Appendix 8 
EQ-5D-3L ................................................................................. 109 
Appendix 9 
Likert Scale for Pruritus Evaluation ........................................... 110 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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 PROTOCOL SYNOPSIS 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Study Location: 
United States, Europe, Japan, and Australia 
Clinical Phase:  
3 
Study Period: 
Planned enrollment period: 24 months  
Planned study period: 36 months  
Study Drug: 
KW-0761 
Comparator Drug: 
Vorinostat (ZOLINZA®) 
Population Size: 
It is anticipated that approximately 317 subjects may be required to enroll in this study in order to achieve the 
necessary 255 progression-free survival (PFS) events for analysis. 
Study Design: 
This is an open-label, multi-center randomized, Phase 3 study with 1:1 randomization of study drug, KW-0761 
versus the comparator, vorinostat. 
Study Population: 
This study will enroll subjects with Stage IB, II-A, II-B, III and IV mycosis fungoides (MF) or Sézary syndrome 
(SS) who have failed at least one prior course of systemic therapy.  
Study Objectives: 
Primary Objective 
• 
To compare the progression free survival of KW-0761 versus vorinostat for subjects with relapsed or 
refractory Cutaneous T-Cell Lymphoma (CTCL). 
Secondary Objectives 
• 
To compare the overall response rate of KW-0761 versus vorinostat in subjects with relapsed or refractory 
CTCL; 
• 
To evaluate and compare improvements in Quality of Life (QoL) measurements, Skindex-29, FACT-G, and 
EQ-5D-3L for subjects receiving KW-0761 versus vorinostat; 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
• 
To evaluate and compare improvements in the Pruritus Evaluation (Likert scale & Itchy QoL) for subjects 
receiving KW-0761 versus vorinostat;  
• 
To estimate the duration of response for both the KW-0761 and vorinostat arms for those subjects with 
relapsed or refractory CTCL responding to treatment; 
• 
To determine if subjects who relapse on vorinostat can achieve response upon cross over to treatment with 
KW-0761;  
• 
To further assess the safety of KW-0761; 
• 
To describe the immunogenicity of KW-0761; 
Exploratory Objectives 
• 
To compare the overall survival of KW-0761 versus vorinostat for subjects with relapsed or refractory 
CTCL.  
• 
To conduct exploratory evaluation of KW-0761 exposure-response relationships. 
Inclusion Criteria: 
1) Voluntarily signed and dated Institutional Review Board / Ethics Committee approved informed 
consent form in accordance with regulatory and institutional guidelines. Written informed consent must 
be obtained prior to performing any study-related procedure; 
Age and Sex 
2) Males and female subjects ≥ 18 years of age at the Pre-treatment Visit, i.e., at the time that written 
informed consent is obtained, except in Japan where subjects must be ≥  20 years of age; 
Target Population 
3) Histologically confirmed diagnosis of MF or SS; 
a. 
For SS (defined as meeting T4 plus B2 criteria), where the biopsy of erythrodermic skin may only 
reveal suggestive but not diagnostic histopathologic features, the diagnosis may be based on either 
a node biopsy or fulfillment of B2 criteria including a clone in the blood that matches that of the 
skin. 
4) Stage IB, II-A, II-B, III and IV; 
5) Subjects who have failed at least one prior course of systemic therapy (e.g., interferon, denileukin 
diftitox, bexarotene, photopheresis, anti-neoplastic chemotherapy, etc.). Psoralen plus ultraviolet light 
therapy (PUVA) is not considered to be a systemic therapy; 
6) Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1; 
7) The subject has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤ 1 
by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
(NCI-CTCAE, v.4.0) excluding the specifications required in 8, 9 and 10 below. 
8) Adequate hematological function:  
a. 
absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3); 
b. platelets ≥ 100,000 cells/μL; (≥ 100,000/mm3); 
c. 
in subjects with known bone marrow involvement, ANC must be ≥ 1,000 cells/μL (≥ 1,000/mm3) 
and platelets ≥ 75,000 cells/μL. (≥ 75,000/mm3). 
9) Adequate hepatic function:  
a. 
bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN), except for subjects 
with Gilbert’s syndrome;  
b. aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 x ULN or ≤ 5.0 x ULN 
in the presence of known hepatic involvement by CTCL.  
10) Adequate renal function:  
a. 
serum creatinine ≤ 1.5 x ULN; 
                                            or  
b. calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault formula. 
11) Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible provided their CD4+ 
cell counts are ≥ 200/mm3. 
12) Subjects with MF and a known history of non-complicated staphylococcus infection/colonization are 
eligible provided they continue to receive stable doses of prophylactic antibiotics. 
13) Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days of 
receiving study medication. 
14) WOCBP must agree to use effective contraception, defined as oral contraceptives, double barrier 
method (condom plus spermicide or diaphragm plus spermicide) or practice true abstinence from 
sexual intercourse (periodic abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation 
methods and withdrawal are not acceptable methods of contraception) during the study and for 
3 months after the last dose. WOCBP includes any female who has experienced menarche and who has 
not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea 
≥ 12 consecutive months without an alternative medical cause); 
15) Male subjects and their female partners of child bearing potential must be willing to use an appropriate 
method of contraception defined as oral contraceptives, double barrier method (condom plus 
spermicide or diaphragm plus spermicide) or practice true abstinence from sexual intercourse (periodic 
abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not 
acceptable methods of contraception) during the study and for 3 months after the last dose. 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
NOTE:  For subjects continuing to receive study treatment as of protocol Amendment 8, the period of 
contraceptive use should be extended to 6 months after the last dose of KW-0761. 
Exclusion Criteria: 
Medical History and Concurrent Diseases 
1) Current evidence of large cell transformation (LCT). Subjects with clinical features suggestive of LCT 
must have a biopsy performed within 4 months prior to Cycle 1 Day 1 to rule out transformed disease. 
Subjects with a history of LCT but without current aggressive disease and no current evidence of LCT 
on pathology in skin or lymph nodes would be eligible; 
2) Diagnosed with a malignancy in the past 2 years. However, subjects with non-melanoma skin cancers, 
melanoma in situ, localized cancer of the prostate with current prostate-specific antigen of 
< 0.1 ng/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of 
the breast with in the past 2 years may enroll as long as there is no current evidence of disease.  
3) Clinical evidence of central nervous system (CNS) metastasis. 
4) Psychiatric illness, disability or social situation that would compromise the subject’s safety or ability to 
provide consent, or limit compliance with study requirements. 
5) Significant uncontrolled intercurrent illness including, but not limited to:  
a. 
uncontrolled infection requiring antibiotics;  
b. clinically significant cardiac disease (class III or IV of the New York Heart Association 
classification);  
c. 
unstable angina pectoris;  
d. angioplasty, stenting, or myocardial infarction within 6 months;  
e. 
uncontrolled hypertension (systolic blood pressure (BP) > 160 mm Hg or diastolic BP 
> 100 mm Hg, found on 2 consecutive measurements separated by a 1-week period) despite 2 anti-
hypertensive medications;  
f. 
clinically significant cardiac arrhythmia; or  
g. uncontrolled diabetes.  
6) Known or tests positive for human immunodeficiency virus, human T-cell leukemia virus, hepatitis B 
or hepatitis C disease. 
7) Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who started taking 
medication at least 30 days prior to the Pre-treatment Visit, and have no active signs of active infection, 
and whose last active infection was more than 6 months ago, may enter the study, and should continue 
to take the prescribed medication for the duration of the study. 
8) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins. 
9) Known active autoimmune disease will be excluded. (For example, Graves’ disease; systemic lupus 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
erythematosus; rheumatoid arthritis; Crohn’s disease; psoriasis). 
10) Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating. 
Prohibited Therapies and/or Medications 
11) Prior treatment with KW-0761. 
12) Prior treatment with vorinostat. Patients who were exposed  to vorinostat for a short time, did not 
progress while on treatment, and did not have intolerable toxicity but were discontinued for another 
reason (e.g., comorbidity) may be permitted to enter the study after discussion with the Medical 
Monitor. 
13) Have had any therapy directed against the subject’s underlying cancer or any investigational 
medications within four weeks of randomization (skin directed treatments, including topicals and 
radiation within 2 weeks of randomization). However, subjects with rapidly progressive malignant 
disease may be enrolled prior to this period after discussion with the Medical Monitor.  
14) Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone equivalent) for at 
least 4 weeks prior to the Pre-treatment Visit may continue use although the investigator should attempt 
to taper the use to the lowest dosage tolerable while on study. Initiation of treatment with systemic 
corticosteroids or increase in dose while on study is not permitted except to treat an infusion reaction 
(see Section 5.2.1.7). Subjects may receive intra-articular corticosteroid injections, intraocular 
corticosteroid drops, inhalation or nasal corticosteroids and replacement doses of systemic 
corticosteroids as needed.  
15) Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to 
the Pre-treatment Visit may continue use at the same dose, although the investigator should attempt to 
taper the use to the lowest dosage tolerable while on study. Initiation of treatment with topical 
corticosteroids while on study is not permitted except to treat an acute rash. 
16) History of allogeneic transplant. 
17) Autologous hematopoietic stem cell transplant within 90 days of the Pre-treatment Visit. 
18) Subjects on any immunomodulatory drug for concomitant or intercurrent conditions other than T-cell 
lymphoma or who have received any of these agents within 4 weeks of treatment, including but not 
limited to the following, will be excluded:  low dose or oral methotrexate; azathioprine; intravenous 
(iv) immunoglobulin; low dose or oral cyclophosphamide; cyclosporine; mycophenolate; infliximab; 
etanercept; leflunomide; adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-β; IL-2 
and natalizumab. 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
17 
 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Methods: 
Subjects will be randomized 1:1 to receive either KW-0761 or vorinostat. Treatment will be administered on an 
outpatient basis. The dose of KW-0761 will be 1.0 mg/kg. The dose of vorinostat will be the recommended dose 
of 400 mg (once daily with food).  
Each treatment cycle is 28 days. Subjects will receive KW-0761 as an iv infusion over at least 1 hour on Days 1, 
8, 15 and 22 of the first cycle and on Days 1 and 15 of subsequent cycles. Vorinostat will be administered orally 
daily beginning on Day 1. 
Duration of Treatment 
Subjects may remain in the treatment phase up until progressive disease (PD), drug intolerance, or unacceptable 
toxicity, or until any of the other criteria for study removal are met. If the subject experiences an overall CR, the 
subject may continue treatment for up to 12 months or until progression, whichever comes first. 
Cross-over to Study Drug KW-0761 
Subjects who have received at least 2 full treatment cycles and demonstrate progression of disease on treatment 
with vorinostat at the 8 week (Cycle 2, Day 26-28) assessment, or anytime thereafter, may cross over to 
treatment with KW-0761 after discussion with Medical Monitor or designee and receipt of approval for cross 
over from KKD. Investigators should strive to maintain subjects on treatment for at least the 8 week period, 
adjusting the dose of vorinostat as needed for toxicities in order to allow sufficient time to see effect. In cases 
where a subject’s disease progresses rapidly (i.e., prior to 8 weeks), the Medical Monitor or designee should be 
contacted and may consider the possibility of early crossover, if appropriate for that subject. All subjects must 
undergo the full extent of disease evaluations (including computed tomography scanning) to document PD prior 
to crossover.  
Study Procedures for Subjects Continuing Study Treatment at the Time of Primary Efficacy Analysis 
and for Ongoing Subjects at the Time of Initial Marketing Authorization 
For subjects who are continuing to receive study treatment at the time of the primary efficacy analysis, 
procedures and assessments are described in Section 7.7.  Procedures to be followed for subjects who are 
ongoing in the study (i.e., subjects who are continuing to receive KW-0761 or who are in safety or survival 
follow-up) at the time of initial marketing authorization are described in Section 7.8. 
Replacement of Subjects 
Subjects will not be replaced. 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
18 
 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Criteria for Evaluation: 
Safety:  The safety of KW-0761 and vorinostat will be determined by reported AEs, changes in physical 
examinations, vital sign measurements, ECGs and laboratory analyses. Safety evaluations will be performed 
throughout the study.  
Efficacy:  Efficacy evaluations will be based on response to treatment (partial response [PR] or better), time to 
PD, duration of overall response, and quality of life. 
Statistical Analysis: 
The following analysis sets will be used in the study: 
• 
Intent-to-Treat (ITT) Set:  Includes all subjects randomized to a therapy and assigned a study number. 
• 
Safety Analysis Set:  Includes all subjects who received at least one dose of the assigned study agent (even 
a partial dose).  
• 
Efficacy Evaluable Set: Includes all subjects who receive the first cycle of treatment and who have baseline 
and the Day 26-28 on-study assessment for response.  
• 
Pharmacokinetic (PK) Analysis Set:  All subjects who provide at least one post-dose KW-0761 
concentration measurement will be included in the PK analysis dataset.  
Evaluation of the data for this study will consist primarily of data listings and summary displays. Demographic 
and other baseline characteristic information will be summarized for the ITT Set. All summaries for the Safety 
Analysis Set will be prepared for each treatment arm. Adverse events will be tabulated by body system, severity, 
and relation to treatment. Similar presentations will be provided for serious adverse events, AEs leading to 
withdrawal from study, and AEs leading to death. The tabulation of laboratory parameters will indicate the 
normal range for each parameter. Each value will be classified as falling above, below, or within the normal 
range.  
Subjects will be evaluated for response in each compartment. Progression-free-survival, overall response, 
duration of response, and QoL will be analyzed. For any time-to-event endpoints, the date of disease progression 
will be determined by both the on-site investigator’s assessment and by independent review (IR). All efficacy 
analyses will be conducted on both the ITT and Efficacy Evaluable sets.  
The primary comparison of PFS between both arms will be performed on the ITT set based upon the results of 
the on-site investigator’s assessment using a stratified Log-rank test at the one-sided 2.5% significance level. 
Stratification is done by disease type, either SS or MF, and disease stage, either IB/II or III/ IV. A similar 
secondary analysis will be performed on the results based on the IR. An IR will review each subject to make a 
determination regarding progression and the date of progression in each compartment. 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
19 
 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Each analysis will also be conducted for the Efficacy Evaluable Set. PFS, which will be analyzed using Kaplan-
Meier survival analysis methods, is defined as the time from the first day of randomization to a treatment arm 
until documented progression or death.  
For PFS events, all deaths will be attributed to progression and, hence, the time to progression will equal the 
time to death and will be uncensored. Subjects who die without a reported prior progression will still be 
considered to have progressed on the day of their death. In the event that a randomized subject withdraws from 
the study for any reason before documented progression, the time from the day of randomization to the last 
tumor assessment (from any compartment) will be used as a censored time point. For all subjects randomized to 
a treatment arm but withdrawing prior to first tumor assessment for any reason other than disease progression, 
the PFS time will be censored at last documented visit.  
ORR will be calculated as the proportion of subjects who are responders (complete response, and PR) and the 
95% exact confidence interval for response will be calculated. 
Since the primary endpoint is PFS, the reference median PFS for vorinostat is assumed to be 169 days. The 
median PFS for KW-0761 therapy is targeted for 254 days, a 50% improvement over this reference median. The 
ITT set is used for this primary analysis. The same analysis conducted using the Efficacy Evaluable set is 
considered secondary. 
Under these assumptions, for the ITT population, a total of 255 PFS events will give 90% power. In the event 
that the study is stopped prior to 255 PFS events are observed, the primary test will be performed at less than 
90% power under the current assumptions. 
A total sample size of 288 may be necessary for 255 PFS events to occur within the projected 36 months of the 
trial. A 10% inflation factor is applied to this total (about 29 subjects) to take into account those subjects that 
may be lost to follow-up prior to documented progression, for a total of 317 enrolled subjects to observe 
255 PFS events. If the 255 PFS events are not observed within 36 months from the start of enrollment the study 
will be stopped at approximately 24 months after the last randomized subject’s first dose. 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
20 
 
Table 1 
Study Procedures:  First Treatment Cycle 
 
Pre-
treatment 
Visit 
First Treatment Cycle 
Procedures 
D 1 
D 8 
D 15 
D 22 
D 26-28a 
Visit Window 
Up to 
Day -30 
 
±2 days 
±2 days 
±2 days 
+ 2 days 
Informed consent 
X 
 
 
 
 
 
Review of subject eligibility 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
Physical examinationb 
X 
X 
 
X 
 
X 
ECOG performance status (PS) 
X 
X 
 
X 
 
X 
Vital signs, Weight 
X 
Xc 
Xc 
Xc 
Xc 
X 
ECG 
X 
 
 
 
 
 
Pregnancy test (within 7 days)  
X 
 
 
 
 
 
Urinalysis 
X 
 
 
 
 
X 
Hematology profile 
X 
Xd 
Xd 
Xd 
Xd 
X 
Chemistry profile 
X 
Xd 
Xd 
Xd 
Xd 
X 
Coagulation profile 
X 
Xd 
 
 
 
 
Thyroid function tests (Free T4, TSH) 
X 
 
 
 
 
X 
Hepatitis B & C, HIV, HTLV-1 
X 
 
 
 
 
 
Flow Cytometric Analysis 
X 
 
 
 
 
X 
Blood sample for determination of 
natural ligands 
X 
 
 
 
 
X 
Serum sample for KW-0761 
concentration assessmente 
 
X 
X 
X 
X 
X 
Saliva sample for genetic analysis 
 
Xf 
 
 
 
 
KW-0761 Administrationg 
 
X 
Xh 
Xh 
Xh 
 
Vorinostat Administration 
 
Xi 
Adverse event assessmentj 
X 
X 
X 
X 
X 
X 
Concomitant medication assessmentk 
X 
X 
X 
X 
X 
X 
CT (diagnostic quality) 
X 
 
 
 
 
X 
Bone marrow aspiration & biopsyl 
X 
 
 
 
 
X 
Skin biopsy for assessment of disease 
Xm 
 
 
 
 
Xn 
Skin biopsy or archival tissue for CCR4 
expressiono 
X 
 
 
 
 
 
Skin photographs 
 
X 
 
 
 
X 
Modified Severity Weighted 
Assessment Tool (mSWAT) 
 
X 
 
 
 
X 
Pruritus Evaluation (Likert Scale & 
Itchy QoL) 
 
X 
 
 
 
X 
Skindex-29 , FACT-G & EQ-5D-3L 
 
X 
 
 
 
X 
Immunogenicityp 
 
X 
 
 
 
X 
Disease Progressionq 
 
Survival statusr 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
21 
 
Footnotes to Table 1 
a: If progression is noted at Day 26-28, visit should take place before initiation of new therapy. In cases where the definition 
of PD or relapse is met but the clinical impression is questionable, subjects may remain on study until the next evaluation 
(4 weeks later if questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after Year 1 if 
questionable finding in lymph nodes or viscera, with at least stable disease in other compartments) to avoid a subject 
being removed prematurely from the study. For subjects receiving a subsequent treatment course, procedures performed 
at this time can also be used to satisfy the Day 1 requirements for the subsequent course, provided they are performed 
within ± 2 days of next KW-0761 administration. For subjects who will not receive subsequent treatment, this visit will be 
considered the final treatment visit and subjects should undergo testing/procedures specified for End-of-treatment visit 
(See Table 3).  
b: Complete physical examination including height at Pre-treatment Visit; brief physical examination of pertinent systems at 
other times. Responses to questions for surveillance of autoimmune type symptoms (See Appendix 4) should be 
documented at time of physical exam. 
c: For subjects receiving KW-0761, vital signs will be checked and recorded prior to the start of each infusion, at the end of 
each infusion and 1 hour after the completion of the infusion. For subjects taking vorinostat, vital signs can be taken 
irrespective of dosing. Weight will be checked with vitals. 
d: Blood can be drawn 1 day prior to visit, if needed, to ensure results are available. In subjects receiving KW-0761, results 
must be reviewed prior to infusion. The platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 
before a subject can receive study drug.  
e: Serum samples will be collected for subjects treated with KW-0761 pre-dose on days indicated (sample collection will 
still be needed even if dosing is not performed at a visit), as applicable. On Day 1, an additional sample should be 
obtained from the arm contralateral to that of study drug administration at the end of infusion (10-15 minutes after 
completion of the infusion) as well. At selected sites, 4 additional samples will be drawn between 6 and 8 hours, and at 
24, 48, and 72 - 96 hours after the first infusion on Day 1. 
f: Samples to be obtained for subjects assigned to KW-0761 as first assigned therapy only. 
g: KW-0761 is to be administered over at least one hour. 
h: If the study visit does not occur within ± 2 days of the scheduled visits, KW-0761 should not be administered at the visit 
and the next dose should be administered at the next timepoint.  
i: Vorinostat is administered orally daily beginning on Day 1 with food. 
j: If a subject who is receiving KW-0761 develops a skin rash, notify KKD and refer to Section 5.2.1.8 to treat and 
document the rash. 
k: Medication taken within 30 days prior to the first dose of study drug, and at any time after the start of treatment until 
30 days after the final study drug administration will be recorded.  
l: To be performed in subjects with cytopenia or other clinical suspicions of bone marrow involvement, at the discretion of 
the investigator. 
m: Subjects with clinical features suggestive of LCT must have a biopsy performed within 4 months prior to Cycle 1/Day 1 
to rule out transformed disease.  
n: Biopsy at the end of the cycle is optional and can be performed at the discretion of the investigator. Analysis of the biopsy 
will be done by a pathologist at the study site. 
o: To be performed for CCR4 expression as determined by IHC. IHC analysis will be performed by central laboratory 
designated by the Sponsor. The paraffin block or a fresh sample, if the study site is unable to process the tissue on the day 
obtained, may be submitted. Submission of unstained slides, while not recommended due to stability concerns with the 
sample, will be accepted. In the event, it is not possible to obtain a skin biopsy, use of an archived sample (taken within 
6 months prior to treatment) may be allowed with prior authorization from the Sponsor. For subjects receiving vorinostat 
who cross over to treatment with KW-0761, investigators are strongly encouraged to perform another biopsy for 
determination of CCR4 expression prior to treatment with KW-0761.  
p: KW-0761 subjects only for determination of anti-KW-0761 antibodies. 
q: Subjects who terminate for reasons other than disease progression or their referring physicians will be contacted every 
3 months (± 14 days) until documented disease progression or death or initiation of alternative therapy.  
r: All subjects or their referring physician will be contacted every 3 months (± 14 days) to ascertain survival status 
following discontinuation of treatment. 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
22 
 
Table 2 
Study Procedures:  Subsequent Cycles in Year 1 
 
Subsequent Cycles 2 through 13a 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 2, 4, 6, 
8, 10, 12)b 
D 26-28
(Cycles 3, 5, 7, 
9, 11, 13)b 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
Physical examinationc 
X 
X 
X 
X 
ECOG PS 
X 
X 
X 
X 
Vital signs, Weight 
Xd 
Xd 
X 
X 
ECG 
 
 
 
 
Urinalysis 
X 
 
 
 
Hematology profile 
Xe 
Xe 
X 
X 
Chemistry profile 
Xe 
Xe 
X 
X 
Coagulation profile 
Xe 
 
 
 
Thyroid function tests (Free T4, TSH) 
 
 
 
X 
Flow Cytometric Analysisf 
 
 
X 
X 
Blood sample for determination of 
natural ligands 
 
 
 
X 
Serum sample for KW-0761 
concentration assessment 
Xg 
Xg 
 
 
KW-0761 Administration 
Xh 
Xh 
 
 
Vorinostat Administration 
Xi 
Adverse event assessmentj 
X 
X 
X 
X 
Concomitant medication assessmentk 
X 
X 
X 
X 
CT (diagnostic quality)f 
 
 
 
X 
Bone marrow aspiration & biopsyl 
 
 
 
X 
Skin biopsy 
 
 
 
Xm 
Skin photographsf 
 
 
X 
X 
Modified Severity Weighted 
Assessment Tool (mSWAT)f 
 
 
X 
X 
Pruritus Evaluation (Likert scale & 
Itchy QoL) 
 
 
X 
X 
Skindex-29, FACT-G & EQ-5D-3L 
 
 
 
X 
Immunogenicityn 
 
 
 
X 
Disease Progressiono 
 
Survival Statusp 
 
a: Subject may remain in treatment phase up until progressive disease, drug intolerance, or unacceptable toxicity, or until 
any of the other criteria for removal (See Section 5.5) are met. At each cycle, the Investigator must minimally have 
reviewed the mSWAT to determine if progression of skin disease has occurred prior to subsequent dosing (see Section 
5.2.1.4). For subjects who are continuing to receive study treatment at the time of the primary efficacy analysis, 
procedures and assessments are described in Section 7.7.  Procedures to be followed for subjects who are ongoing in the 
study at the time of initial marketing authorization are described in Section 7.8. 
 
 
 
 
 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
23 
 
Footnotes to Table 2 (continued). 
b: For subjects receiving a subsequent treatment course, procedures performed at this time can also be used to satisfy the 
Day 1 requirements for the subsequent course, provided they are performed within ± 2 days of next KW-0761 
administration. For subjects who will not receive subsequent treatment, this visit will be considered the final treatment 
visit and subjects should undergo testing/procedures specified for End-of-treatment visit (See Table 3). If progression is 
noted at Day 26-28, visit should take place before initiation of new therapy. In cases where the definition of PD or relapse 
is met but the clinical impression is questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after Year 1 if questionable finding in  
lymph nodes or viscera, with at least stable disease in other compartments) to avoid a subject being removed prematurely 
from the study.  
c: Brief physical examination of pertinent systems to be performed during subsequent treatment cycles. Complete physical 
exam to be performed at End of Treatment visit. Responses to questions for surveillance of autoimmune type symptoms 
(See Appendix 4) should be documented at time of physical exam. 
d: For subjects receiving KW-0761, vital signs will be checked and recorded prior to the start of each infusion, at the end of 
each infusion and 1 hour after the completion of the infusion. For subjects taking vorinostat, vital signs can be taken 
irrespective of dosing. Weight will be checked with vitals. 
e: Blood can be drawn 1 day prior to visit, if needed, to ensure results are available. In subjects receiving KW-0761, results 
must be reviewed prior to infusion. The platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 
before a subject can receive study drug. 
f: If clinical progression is noted at any time prior to the scheduled assessments for efficacy, CT, mSWAT, skin 
photographs and flow cytometry assessments should be done at that time to fully document disease progression, i.e., 
Global Composite Response Score. CT must be performed even if previously negative at baseline. 
g: Serum samples for PK assessment should be collected for subjects treated with KW-0761 prior to infusion of KW-0761 in 
Cycles 2 and 3 (sample collection will still be needed even if dosing is not performed at a visit). 
h: KW-0761 is to be administered over at least one hour. 
i: Vorinostat is administered orally daily beginning on Day 1 with food. 
j: If a subject who is receiving KW-0761 develops a skin rash, notify KKD and refer to Section 5.2.1.8 to treat and 
document the rash. 
k: Medication taken at any time after the start of treatment until 30 days after the final study drug administration will be 
recorded.  
l: To be performed in subjects with cytopenia or other clinical suspicions of bone marrow involvement, at the discretion of 
the investigator. If a bone marrow biopsy was performed at baseline and determined to unequivocally be indicative of 
lymphomatous involvement, then to confirm a global CR where blood assessment now meets criteria for B0, a repeat 
bone marrow biopsy must show no residual disease or the response should be considered a PR only (See Table 7.2.2-1). 
m: Biopsies at the end of the cycle and to confirm a CR (See Table 7.2.1-3) are optional and can be performed at the 
discretion of the investigator. Analysis of these biopsies will be done by a pathologist at the study site. 
n: KW-0761 subjects only for determination of anti-KW-0761 antibodies and concentration of KW-0761. 
o: Subjects who terminate for reasons other than disease progression or their referring physicians will be contacted every 
3 months (± 14 days) until documented disease progression or death or initiation of alternative therapy.  
p: All subjects or their referring physician will be contacted every 3 months (± 14 days) to ascertain survival status 
following discontinuation of treatment. 
 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
24 
 
Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 
14, 16, 
18, 20, 
etc)b 
D 26-28  
(Cycles 15, 
17, 19, 21, 
etc)b 
D 26-28  
Q 16 
wks 
(Cycles 
17, 21, 
etc) 
End-of-
treatment  
visit 
Follow-
upc 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
+ 5 days 
Within 30 
days of last 
dose 
 
Physical examinationd 
X 
X 
X 
X 
 
X 
 
ECOG PS 
X 
X 
X 
X 
 
X 
 
Vital signs, Weight 
Xe 
Xe 
X 
X 
 
X 
 
ECG 
 
 
 
 
 
X 
 
Urinalysis 
X 
 
 
 
 
X 
 
Hematology profile 
Xf 
Xf 
X 
X 
 
X 
 
Chemistry profile 
Xf 
Xf 
X 
X 
 
X 
 
Coagulation profile 
Xf 
 
 
 
 
 
 
Thyroid function tests 
(Free T4, TSH) 
 
 
 
X 
 
X 
 
Flow Cytometric 
Analysisg 
 
 
X 
X 
 
 
 
Blood sample for 
determination of 
natural ligands 
 
 
 
X 
 
 
 
Serum sample for 
KW-0761 
concentration 
assessment 
 
 
 
 
 
X 
 
KW-0761 
Administration 
Xh 
Xh 
 
 
 
 
 
Vorinostat 
Administration 
Xi 
 
 
 
Adverse event 
assessmentj 
X 
X 
X 
X 
 
X 
Xk 
Concomitant 
medication assessmentl 
X 
X 
X 
X 
 
X 
X 
CT (diagnostic quality)g 
 
 
 
 
X 
 
 
Bone marrow 
aspiration & biopsym 
 
 
 
X 
 
 
 
Skin biopsy 
 
 
 
Xn 
 
 
 
Skin photographsg 
 
 
X 
X 
 
 
 
Modified Severity 
Weighted Assessment 
Tool (mSWAT)g 
 
 
X 
X 
 
 
 
Pruritus Evaluation 
(Likert scale & Itchy 
QoL) 
 
 
X 
X 
 
 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
25 
 
Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 
14, 16, 
18, 20, 
etc)b 
D 26-28  
(Cycles 15, 
17, 19, 21, 
etc)b 
D 26-28  
Q 16 
wks 
(Cycles 
17, 21, 
etc) 
End-of-
treatment  
visit 
Follow-
upc 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
+ 5 days 
Within 30 
days of last 
dose 
 
Skindex-29, FACT-G 
& EQ-5D-3L 
 
 
 
X 
 
X 
 
Immunogenicityo 
 
 
 
 
 
X 
 
CD4, CD8 (for 
KW-0761 subjects) 
 
 
 
 
 
Xp 
Xp 
Disease Progressionq 
 
Survival Statusr 
 
a: Subject may remain in treatment phase up until progressive disease, drug intolerance or unacceptable toxicity, or until any 
of the other criteria for removal (See Section 5.5) are met. At each cycle, the investigator must minimally have reviewed 
the mSWAT to determine if progression of skin disease has occurred prior to subsequent dosing (see Section 5.2.1.4). For 
subjects who are continuing to receive study treatment at the time of the primary efficacy analysis, pending notification 
by the Sponsor, subjects may be followed according to institutional standard of care for subsequent assessments of 
treatment efficacy as described in Section 7.7.  Procedures to be followed for subjects who are ongoing in the study at the 
time of initial marketing authorization are described in Section 7.8. 
b: For subjects receiving a subsequent treatment course, procedures performed at this time can also be used to satisfy the 
Day 1 requirements for the subsequent course, provided they are performed within ± 2 days of next KW-0761 
administration. For subjects who will not receive subsequent treatment, this visit will be considered the final treatment 
visit and subjects should undergo testing/procedures specified for End-of-treatment visit. If progression is noted at Day 
26-28, visit should take place before initiation of new therapy. In cases where the definition of PD or relapse is met but 
the clinical impression is questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after Year 1 if questionable finding in 
lymph nodes or viscera, with at least stable disease in other compartments) to avoid a subject being removed prematurely 
from the study.  
c: For subjects going off treatment after achieving a CR, refer to Section 7.6 for study procedures and timing. 
d: Brief physical examination of pertinent systems to be performed during subsequent treatment cycles. Complete physical 
exam to be performed at End of Treatment visit. Responses to questions for surveillance of autoimmune type symptoms 
(See Appendix 4) should be documented at time of physical exam. 
e: For subjects receiving KW-0761, vital signs will be checked and recorded prior to the start of each infusion, at the end of 
each infusion and 1 hour after the completion of the infusion. For subjects taking vorinostat, vital signs can be taken 
irrespective of dosing. Weight will be checked with vitals. 
f: Blood can be drawn 1 day prior to visit, if needed, to ensure results are available. In subjects receiving KW-0761, results 
must be reviewed prior to infusion. The platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 
before a subject can receive study drug. 
 
 
 
 

Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
26 
 
Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 
14, 16, 
18, 20, 
etc)b 
D 26-28  
(Cycles 15, 
17, 19, 21, 
etc)b 
D 26-28  
Q 16 
wks 
(Cycles 
17, 21, 
etc) 
End-of-
treatment  
visit 
Follow-
upc 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
+ 5 days 
Within 30 
days of last 
dose 
 
Footnotes to Table 3 continued. 
g: If clinical progression is noted at any time prior to the scheduled assessments for efficacy, CT, mSWAT, skin 
photographs and flow cytometry assessments should be done at that time to fully document disease progression, i.e., 
Global Composite Response Score. CT must be performed even if previously negative at baseline.  
h: KW-0761 is to be administered over at least one hour. 
i: Vorinostat is administered orally daily beginning on Day 1 with food. 
j: If a subject who is receiving KW-0761 develops a skin rash, notify KKD and refer to Section 5.2.1.8 to treat and 
document the rash. 
k: Adverse events will be collected every 30 days (± 7 days) for up to 90 days after the last dose of study drug or initiation 
of alternative therapy. In all subjects who cross over from vorinostat to KW-0761, the causality should be assessed for 
both drugs for 30 days after vorinostat was stopped (or later if the event is considered to be related to vorinostat).   
l:  Medication taken at any time after the start of treatment until 30 days after the final study drug administration will be 
recorded. A medication taken during follow-up will also be recorded if it is used to treat an AE or is temporally associated 
with an AE and may have a causal relationship. 
m: To be performed in subjects with cytopenia or other clinical suspicions of bone marrow involvement, at the discretion of 
the investigator. If a bone marrow biopsy was performed at baseline and determined to unequivocally be indicative of 
lymphomatous involvement, then to confirm a global CR where blood assessment now meets criteria for B0, a repeat 
bone marrow biopsy must show no residual disease or the response should be considered a PR only (See Table 7.2.2-1) 
n: Biopsies at the end of the cycle and to confirm a CR (See Table 7.2.1-3) are optional and can be performed at the 
discretion of the investigator. Analysis of these biopsies will be done by pathologist at the study site. 
o: KW-0761 subjects only for determination of anti-KW-0761 antibodies. 
p: If CD4 and CD8 counts are less than 200/mm3 at the End-of-treatment visit, they will be followed every 3 months 
(±14 days) until they return to at least 200/mm3, initiation of alternative therapy or 1 year, whichever comes first. 
Assessments will be performed at the study site. 
q: Subjects who terminate for reasons other than disease progression or their referring physicians will be contacted every 
3 months (± 14 days) until documented disease progression or death or initiation of alternative therapy.  
r: All subjects or their referring physician will be contacted every 3 months (± 14 days) to ascertain survival status following 
discontinuation of treatment. 
 
 

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List of Abbreviations 
Abbreviations 
Ab 
antibody 
ADCC 
antibody dependent cellular cytotoxicity 
AE 
adverse event 
Ag 
antigen 
ALT 
Alanine transaminase 
ANC 
absolute neutrophil count 
ASCO 
American Society of Clinical Oncology  
ASH 
American Society of Hematology 
AST 
aspartate transaminase 
ATL 
adult T-cell leukemia-lymphoma 
β-HCG 
beta-human chorionic gonadotrophin 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CCR4 
CC chemokine receptor 4, chemokine (C-C motif) receptor 4 
CNS 
central nervous system 
CR 
complete response 
CS 
clinically significant 
CT 
computed tomography 
CTA 
Clinical Trial Authorization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTCL 
cutaneous T-cell lymphoma 
CTIVRS 
ClinTrak Interactive Voice/Web Response System 
DOR 
duration of response 
DSMB 
Data Safety Monitoring Board  
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EORTC 
European Organization for Research and Treatment of Cancer  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HDAC 
histone deacetylase  
HEENT 
head, eyes, ears, nose and throat 
HIV 
human immunodeficiency virus 
HSCT 
hematopoetic stem cell transplantation 
HTLV-1 
human T-cell lymphotropic virus type-1 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization 
IHC 
immunohistochemistry 
IND 
Investigational New Drug Application 

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Abbreviations 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IR 
Independent Review/Reviewer  
ISCL 
International Society of Cutaneous Lymphomas  
ITT 
Intent-to-Treat 
iv 
intravenous 
KKD 
Kyowa Kirin Pharmaceutical Development, Inc. 
KW-0761 
humanized monoclonal antibody against CCR4 
LDH 
lactate dehydrogenase 
Mab 
monoclonal antibody 
MDC 
macrophage derived chemokine 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
mycosis fungoides 
mSWAT 
modified Severity Weighted Assessment Tool 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NCS 
not clinically significant 
NHL 
non-Hodgkin’s Lymphoma 
NYHA 
New York Heart Association  
ORR 
objective response rate 
OS 
overall survival  
PD 
progressive disease 
PDF 
Portable Document Format 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PR 
partial response 
PS 
performance status 
PT 
prothrombin time 
PTCL 
peripheral T-cell lymphoma 
PTT 
partial thromboplastin time 
QoL 
Quality of Life 
SAE 
serious adverse event 
SD 
stable disease 
SEER 
Surveillance Epidemiology and End Results 
SGOT  
serum glutamic oxaloacetic-transaminase  
SGPT  
serum glutamic pyruvic-transaminase  
SJS 
Stevens-Johnson syndrome 
SPD 
sum of the product of the diameters 
SS 
Sézary Syndrome 
TARC 
thymus- and activation-regulated chemokine 
TBSA 
total body surface area 
TEAE 
treatment-emergent adverse event 
TEN 
toxic epidermal necrolysis 
TTP 
time to progression 
ULN 
upper limit of normal 
US 
United States  

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Abbreviations 
USCLC 
United States Cutaneous Lymphoma Consortium  
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 
Definition of Terms 
pH 
hydrogen ion concentration; negative logarithm of hydrogen ion activity 
p.r.n. 
as needed 
QT interval  
in electrocardiography, the time from the beginning of the QRS complex to the end of the T 
wave. 
QTc interval 
QT interval corrected for heart rate  
 

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1 
BACKGROUND AND RATIONALE  
1.1 
Cutaneous T-Cell Lymphomas 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
  
 
 
 
 
 
  
 
 
 
 
  

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1.2 
Treatment of Cutaneous T-cell Lymphomas 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.  
1.3 
Chemokine Receptor 4 and T-Cell Malignancies 
 
 
 
 
 
 

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1.4 
KW-0761 (mogamulizumab) 
 
 
 
 
 
 
 
1.5 
Safety and Efficacy of KW-0761 
 
 
 
 
 
 
 
 
 
 

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1.6 
Vorinostat (ZOLINZA®) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.7 
Rationale  
 
 
 
 
 
 
 
 
 
 
 
  
 
 

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2 
OBJECTIVES 
2.1 
Primary Objectives 
The primary objective of this study will be: 
• 
To compare the progression free survival of KW-0761 versus vorinostat for subjects with 
relapsed or refractory CTCL.  
2.2 
Secondary Objectives 
The secondary objectives will be: 
• 
To compare the overall response rate of KW-0761 versus vorinostat in subjects with 
relapsed or refractory CTCL; 
• 
To evaluate and compare improvements in QoL measurements, Skindex-29, FACT-G and 
EQ-5D-3L for subjects receiving KW-0761 versus vorinostat; 
• 
To evaluate and compare improvements in the Pruritus Evaluation (Likert scale & Itchy 
QoL) for subjects receiving KW-0761 versus vorinostat;  
• 
To estimate the duration of response for both the KW-0761 and vorinostat arms for those 
subjects with relapsed or refractory CTCL responding to treatment; 
• 
To determine if subjects who relapse on vorinostat can achieve response upon cross over 
to treatment with KW-0761;  
• 
To further assess the safety of KW-0761; 
• 
To describe the immunogenicity of KW-0761. 

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2.3 
Exploratory Objectives 
• 
To compare the overall survival of KW-0761 versus vorinostat for subjects with relapsed 
or refractory CTCL;  
• 
To conduct exploratory evaluation of KW-0761 exposure-response relationships. 
3 
STUDY POPULATION 
3.1 
Subject Selection 
This study will enroll subjects with CTCL who have failed at least one prior course of 
systemic therapy. This should be adequately documented in the subject’s medical record. 
3.2 
Inclusion Criteria 
Subject must meet the following criteria for inclusion in this study: 
Signed Written Informed Consent 
1) Voluntarily signed and dated Institutional Review Board (IRB)/ Ethics Committee 
approved informed consent form in accordance with regulatory and institutional 
guidelines. Written informed consent must be obtained prior to performing any 
study-related procedure; 
Age and Sex 
2) Males and female subjects ≥ 18 years of age at the Pre-treatment Visit, i.e., at the 
time that written informed consent is obtained, except in Japan where subjects must 
be ≥ 20 years of age; 
Target Population 
3) Histologically confirmed diagnosis of MF or SS; 
a. For SS (defined as meeting T4 plus B2 criteria), where the biopsy of 
erythrodermic skin may only reveal suggestive but not diagnostic 
histopathologic features, the diagnosis may be based on either a node biopsy or 
fulfillment of B2 criteria including a clone in the blood that matches that of the 
skin (Olsen, 2011).  
4) Stage IB, II-A, II-B, III and IV (Olsen, 2011) (see Appendix 1); 
5) Subjects who have failed at least one prior course of systemic therapy (e.g., 
interferon, denileukin diftitox, bexarotene, photopheresis, anti-neoplastic 
chemotherapy, etc.). Psoralen plus ultraviolet light therapy (PUVA) is not 
considered to be a systemic therapy; 
6) Eastern Cooperative Oncology Group (ECOG) performance status score (Oken, 
1982) of ≤ 1 (see Appendix 2). 
7) The subject has resolution of all clinically significant toxic effects of prior cancer 
therapy to Grade ≤ 1 by the National Cancer Institute Common Terminology 

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Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0) excluding the 
specifications required in 8, 9 and 10 below. 
8) Adequate hematological function:  
a. absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3); 
b. platelets ≥ 100,000 cells/μL (≥ 100,000/mm3); 
c. in subjects with known bone marrow involvement, ANC must be 
≥ 1,000 cells/μL (≥ 1,000/mm3) and platelets ≥ 75,000 cells/μL (≥ 75,000/mm3).  
9) Adequate hepatic function:  
a. bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN), 
except for subjects with Gilbert’s syndrome;  
b. aspartate transaminase (AST) and alanine transaminase (ALT) each 
≤ 2.5 x ULN or ≤ 5.0 x ULN in the presence of known hepatic involvement by 
CTCL.  
10) Adequate renal function:  
a. serum creatinine ≤ 1.5 x ULN  
                                            or  
b. calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault formula. 
11) Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible 
provided their CD4+ cell counts are ≥ 200/mm3. 
12) Subjects with MF and a known history of non-complicated staphylococcus 
colonization/infection are eligible provided they continue to receive stable doses of 
prophylactic antibiotics. 
13) Women of childbearing potential (WOCBP) must have a negative pregnancy test 
within 7 days of receiving study medication. 
14) WOCBP must agree to use effective contraception, defined as oral contraceptives, 
double barrier method (condom plus spermicide or diaphragm plus spermicide) or 
practice true abstinence from sexual intercourse (periodic abstinence, e.g., calendar, 
ovulation, symptothermal, post-ovulation methods and withdrawal are not 
acceptable methods of contraception) during the study and for 3 months after the 
last dose. WOCBP includes any female who has experienced menarche and who has 
not undergone successful surgical sterilization or is not postmenopausal (defined as 
amenorrhea ≥ 12 consecutive months without an alternative medical cause). 
15) Male subjects and their female partners of child bearing potential must be willing to 
use an appropriate method of contraception defined as oral contraceptives, double 
barrier method (condom plus spermicide or diaphragm plus spermicide) or practice 
true abstinence from sexual intercourse (periodic abstinence, e.g., calendar, 
ovulation, symptothermal, post-ovulation methods and withdrawal are not 
acceptable methods of contraception) during the study and for 3 months after the 
last dose. 
NOTE:  For subjects continuing to receive study treatment as of protocol Amendment 8, the 
period of contraceptive use should be extended to 6 months after the last dose of KW-0761. 

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3.3 
Exclusion Criteria 
Subjects with any of the following will be excluded from the study:  
Medical History and Concurrent Diseases 
1) Current evidence of large cell transformation (LCT). Subjects with clinical features 
suggestive of LCT must have a biopsy performed within 4 months prior to Cycle 1 
Day 1 to rule out transformed disease. Subjects with a history of LCT but without 
current aggressive disease and no current evidence of LCT on pathology in skin or 
lymph nodes would be eligible. 
2) Diagnosed with a malignancy in the past 2 years. However, subjects with non-
melanoma skin cancers, melanoma in situ, localized cancer of the prostate with 
current prostate-specific antigen of < 0.1 ng/mL, treated thyroid cancer or cervical 
carcinoma in situ or ductal/lobular carcinoma in situ of the breast with in the past 
2 years may enroll as long as there is no current evidence of disease.  
3) Clinical evidence of central nervous system (CNS) metastasis. 
4) Psychiatric illness, disability or social situation that would compromise the subject’s 
safety or ability to provide consent, or limit compliance with study requirements. 
5) Significant uncontrolled intercurrent illness including, but not limited to:  
a. uncontrolled infection requiring antibiotics;  
b. clinically significant cardiac disease (class III or IV of the New York Heart 
Association [NYHA] classification, see Appendix 3);  
c. unstable angina pectoris;  
d. angioplasty, stenting, or myocardial infarction within 6 months;  
e. uncontrolled hypertension (systolic blood pressure (BP) > 160 mm Hg or diastolic 
BP > 100 mm Hg, found on 2 consecutive measurements separated by a 1-week 
period) despite 2 anti-hypertensive medications;  
f. clinically significant cardiac arrhythmia or  
g. uncontrolled diabetes.  
6) Known or tests positive for human immunodeficiency virus (HIV), human T-cell 
lymphotropic virus (HTLV-1), hepatitis B or hepatitis C disease.  
7) Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who 
started taking medication at least 30 days prior to the Pre-treatment Visit, and have no 
active signs of active infection, and whose last active infection was more than 
6 months ago, may enter the study, and should continue to take the prescribed 
medication for the duration of the study. 
8) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins. 
9) Known active autoimmune disease will be excluded. (For example, Graves’ disease; 
systemic lupus erythematosus; rheumatoid arthritis; Crohn’s disease; psoriasis). 
10) Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or 
lactating. 

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Prohibited Therapies and/or Medications 
11) Prior treatment with KW-0761. 
12) Prior treatment with vorinostat. Patients who were exposed to vorinostat for a short 
time, did not progress while on treatment, and did not have intolerable toxicity but 
were discontinued for another reason (e.g., comorbidity) may be permitted to enter the 
study after discussion with the Medical Monitor. 
13) Have had any therapy directed against the subject’s underlying cancer or any 
investigational medications within four weeks of randomization (skin directed 
treatments, including topicals and radiation within 2 weeks of randomization). 
However, subjects with rapidly progressive malignant disease may be enrolled prior 
to this period after discussion with the Medical Monitor. 
14) Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone 
equivalent) for at least 4 weeks prior to the Pre-treatment Visit may continue use 
although the investigator should attempt to taper the use to the lowest dosage tolerable 
while on study. Initiation of treatment with systemic corticosteroids or increase in 
dose while on study is not permitted except to treat an infusion reaction (see Section 
5.2.1.7). Subjects may receive intra-articular corticosteroid injections, intraocular 
corticosteroid drops, inhalation or nasal corticosteroids and replacement doses of 
systemic corticosteroids as needed.  
15) Subjects on a stable dose of medium or low potency topical corticosteroids for at least 
4 weeks prior to the Pre-treatment Visit may continue use at the same dose, although 
the investigator should attempt to taper the use to the lowest dosage tolerable while on 
study. Initiation of treatment with topical corticosteroids while on study is not 
permitted except to treat an acute rash. 
16) History of allogeneic transplant. 
17) Autologous hematopoietic stem cell transplant within 90 days of the Pre-treatment 
Visit. 
18) Subjects on any immunomodulatory drug for concomitant or intercurrent conditions 
other than T-cell lymphoma or who have received any of these agents within 4 weeks 
of treatment, including but not limited to the following, will be excluded:  low dose or 
oral methotrexate; azathioprine; iv immunoglobulin; low dose or oral 
cyclophosphamide; cyclosporine; mycophenolate; infliximab; etanercept; 
leflunomide; adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-β; 
IL-2 and natalizumab.  
3.4 
Eligibility for Cross-over to KW-0761 
Subjects who are randomized to the vorinostat arm may cross over to KW-0761 upon 
progression or in the event of intolerable toxicity (see Section 5.3). Crossover may take place 
following discussion with the Medical Monitor or designee and receipt of approval for cross 
over from Kyowa Kirin Pharmaceutical Development, Inc. (KKD). However, they must 

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continue to fulfill inclusion criteria 6 through 15, and will be excluded if they fulfill the 
exclusion criteria, except for exclusion criteria 1, 12 and 13 (refer to Section 3.3).  
4 
INVESTIGATIONAL PLAN 
4.1 
Overview of Study Design 
This is an open-label, multi-center randomized, Phase 3 study with 1:1 randomization of 
study drug, KW-0761 versus the comparator, vorinostat. 
4.2 
Number of Subjects 
Approximately 317 subjects may enroll in this study over a period of 24 months. The primary 
analysis will be conducted when 255 total progression-free survival (PFS) events have been 
observed or 24 months after the last randomized subject’s first dose, whichever comes first. 
4.3 
Investigational Centers 
It is anticipated that approximately 75 investigational centers in the US, Europe, Japan and 
Australia will participate in this study.  
5 
TREATMENT PLAN 
5.1 
Assignment to Study  
After a subject signs consent, screening numbers should be assigned by the investigator (or 
designee) using ClinTrak Interactive Voice/Web Response System (CTIVRS). Once 
assigned, numbers for any screen failures or non-treated, non-evaluable, or discontinued 
subjects will not be re-used. 
A subject who meets all entry criteria will be randomized in a 1:1 ratio to receive KW-0761 
or vorinostat. The randomization to treatment groups will be stratified by disease type (MF or 
SS) and disease stage (IB/II or III/IV). When a subject is determined to be eligible for 
randomization the investigator (or designee) will contact CTIVRS to obtain the 
randomization assignment for the subject. If a subject is randomized in error, or a dosing 
error occurs, KKD (or designee) should be notified as soon as the error is discovered. 
5.2 
Study Treatments 
In this protocol, study treatments are KW-0761 and vorinostat. Subjects will be randomized 
to the study drug, KW-0761 or comparator, vorinostat, in a 1:1 ratio. 

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5.2.1 
Study Drug: KW-0761 (mogamulizumab) 
Treatment can be administered on an outpatient basis. Subjects will receive 1.0 mg/kg of 
KW-0761 as an iv infusion over at least 1 hour on Days 1, 8, 15, and 22 of the first cycle and 
on Days 1 and 15 of subsequent cycles. No other investigational or commercial agents or 
therapies other than the study treatment and those described in Section 5.4.1 may be 
administered with the intent to treat the subject’s malignancy. 
5.2.1.1 
Premedication Prior to KW-0761 Infusion 
It is recommended that subjects be premedicated with acetaminophen or paracetamol orally 
and diphenhydramine 50 mg iv (or equivalent anti-histamine) before the first KW-0761 
infusion. For subjects who experience an infusion related reaction, premedication is 
recommended prior to every subsequent infusion. 
5.2.1.2 
Definition of Treatment Cycle 
Each treatment cycle is 28 days.  
5.2.1.3 
Delays in Dosing 
During the first treatment cycle, KW-0761 should be administered beginning on Day 1 and 
within ± 2 days of the other scheduled visits (i.e., Days 8, 15 and 22 during Cycle 1; Day 15 
during subsequent cycles). If the study visit does not occur within this visit window, 
KW-0761 should not be administered at the visit and the next dose should be administered at 
the next timepoint. 
A subject’s next cycle should begin within 2 weeks of the completion of the prior cycle. The 
start of a new cycle may be delayed to allow resolution of treatment-related toxicities or for 
non-medical reasons (holidays, vacations, etc.). Delay of the start of a new cycle greater than 
2 weeks must be discussed with the Medical Monitor or designee. 
5.2.1.4 
Duration of Treatment 
Subjects may remain in the treatment phase up until PD, drug intolerance or unacceptable 
toxicity, or until any of the other criteria for study removal are met, as defined in Section 5.5. 
Except in cases of unacceptable toxicity or drug intolerance, every effort should be made to 
ensure the subject remains in the study until disease progression (See Section 7.2.4, regarding 
definition of disease progression). 
At each cycle, the investigator must minimally have reviewed the modified Severity 
Weighted Assessment Tool (mSWAT) to determine if progression of skin disease has 

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occurred prior to subsequent dosing. Ideally, results of flow cytometry and CT assessment, as 
applicable, should be reviewed at this visit as well. However, it is understood that these 
results may not be reported for several days and may not be available. Once those results are 
obtained evidence of progression in all compartments should be determined. 
In cases where the definition of PD or relapse is met but the clinical impression is 
questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after 
Year 1 if questionable finding in lymph nodes or viscera, with at least stable disease in other 
compartments) to avoid a subject being removed prematurely from the study. If PD is 
confirmed at this subsequent evaluation, subject should be discontinued from treatment. If PD 
is not confirmed at this subsequent evaluation, the subject may remain on study. 
This course of action only applies to cases where the clinical impression is questionable; 
subjects in frank or obvious PD in any compartment should be discontinued from protocol 
therapy. 
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (computed tomography [CT], mSWAT, skin photographs and flow cytometry) 
should be done at that time to fully document disease progression. CT must be performed 
even if previously negative at baseline.  
If the subject experiences an overall CR, the subject may continue treatment for up to 
12 months or until progression, whichever comes first.  
For subjects who are continuing to receive study treatment at the time of the primary efficacy 
analysis, procedures and assessments are described in Section 7.7. Procedures to be followed 
for subjects who are continuing to receive KW-0761 at the time of initial marketing 
authorization are described in Section 7.8. 
5.2.1.5 
Replacement of Subjects 
Subjects will not be replaced.  
5.2.1.6 
Dose Modifications 
No dose modifications of the KW-0761 will be permitted in this study.  
5.2.1.7 
Treatment of Hypersensitivity-Like Reactions 
It may be difficult to differentiate an infusion reaction from a true hypersensitivity (i.e., 
allergic) reaction. If a reaction occurs during infusion of KW-0761, investigators may use the 
following guidelines to best treat the subject’s symptoms: 

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Grade 1/2: 
• 
Stop the infusion for 15–30 minutes; 
• 
Acetaminophen or paracetamol orally and diphenhydramine 50 mg iv or equivalent 
anti-histamine may be administered;  
• 
If symptoms abate, re-start the infusion at one-half the previous rate; 
• 
If symptoms do not abate after 30 minutes, discontinue that day’s treatment. Additional 
medical measures, such as administration of corticosteroids (see below) may be 
considered for reactions that do not abate after 30 minutes. 
Grade 3 
• 
Stop the infusion for 15–30 minutes; 
• 
Consider administering the following: 
– Acetaminophen or paracetamol orally;  
– Diphenhydramine 50 mg iv or an equivalent anti-histamine; 
– Dexamethasone 20 mg iv or an equivalent corticosteroid; 
– Albuterol or salbutamol inhaler 2 puffs p.r.n. for bronchospasm or an equivalent 
bronchodilator; 
– O2 by nasal cannula.  
• 
Additional agents may be administered per institutional guidelines for the treatment of 
infusion reactions; 
• 
If symptoms abate, re-start the infusion at one-half the previous rate; 
• 
If symptoms do not abate after 30 minutes, discontinue the subject from the study.  
Grade 4 
• 
Administration of the agents specified for a Grade 3 infusion reaction above should be 
considered. 
• 
Any subject who experiences a Grade 4 infusion reaction is to be discontinued from the 
study. 
If a reaction with severity of Grade 2 or higher occurs upon re-challenge with KW-0761, or if 
in the opinion of the investigator the reaction represents a true hypersensitivity (i.e., allergic) 
reaction of Grade 2 or higher, KW-0761 should be stopped and not restarted and the subject 
should be discontinued from the study. 
If an infusion reaction occurs, a serum sample should be obtained and sent to the designated 
central laboratory for analysis of anti-KW-0761 antibodies.  (As of Amendment 10, central 
laboratory analysis of samples will no longer be performed [see Section 7.8].) 

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If an infusion reaction occurs, the duration of administration of KW-0761 should be increased 
to 2 hours for the next 2 infusions. Subsequent infusion duration may be 1 to 2 hours, as 
tolerated. 
For infusion reactions occurring after completion of the infusion, administration of the agents 
specified for a Grade 3 infusion reaction above should be considered, along with any other 
medical intervention stipulated in institutional guidelines for the treatment of infusion 
reactions. 
Any subject who experiences an infusion reaction requiring the administration of systemic 
vasopressors or that results in hospitalization (directly due to infusion reaction symptoms) of 
the subject is to be removed from the study. 
5.2.1.8 
Treatment Emergent Skin Rash 
In the event a subject develops a treatment emergent skin rash, the following measures must 
be taken to appropriately document the event. 
Patients should be closely monitored for symptoms or signs that suggest SJS or TEN. 
If they occur, mogamulizumab should be interrupted and treatment should not restart 
unless SJS or TEN is ruled out and cutaneous reaction has resolved to Grade 1 or less. 
Initial Work-up of All Skin Rashes (new and re-challenge) 
1) Notify KKD of the skin rash. 
2) Photograph the rash. (As of Amendment 8, collection of photographs is no longer 
required.) 
3) If the rash is ≥ Grade 2 or if the affected area cannot be differentiated from a new area 
of lymphoma, a biopsy must be performed. Biopsy the rash as well as an area of skin 
unaffected by the rash in order to compare possible drug eruption to background 
lymphoma involved skin. If the rash is Grade 1 and topical steroids are to be applied, 
the rash must be biopsied prior to steroid treatment. 
4) Confer with Medical Monitor or designee after completion of one week of treatment 
with topical corticosteroids to assess response to treatment.  
5) Forward all results to Medical Monitor and discuss with Medical Monitor or designee 
a treatment plan and medical follow up. 
6) Biopsy should be read by the dermatopathologist at the study center. Additional 
sample should be sent to the laboratory designated by the Sponsor for central review 
as well. Specific instructions for sample preparation and handling for central 
laboratory will be provided in the Laboratory Manual. (As of Amendment 10, central 
laboratory analysis of samples will no longer be performed [see Section 7.8].) 
7) If biopsy indicates that rash is a drug eruption record appropriately as AE/SAE. If 
biopsy indicates that rash is lymphoma, do not record as an AE. 

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Rash Treatment Guidelines (after initial work-up): 
Grade 1 Rash (drug related or non-drug related) 
1) Treatment with KW-0761 may continue. 
2) Treat rash with topical corticosteroids as needed. 
Grade 2 or above Rash (drug related) 
1) Treatment with KW-0761 must be stopped. 
2) Treat rash with 2-week course of topical corticosteroids.  
3) After 2-week course, re-assess rash per the steps outlined in initial assessment; if 
resolved completely or to Grade 1, KW-0761 treatment may be resumed. If not 
resolved, contact the Medical Monitor for further discussion. 
Grade 2 or above rash on Re-challenge 
1) If rash recurs and becomes a Grade 3, the subject must be discontinued from the trial 
and the rash work up above must be completed. 
2) If the rash recurs at a Grade 2, follow the steps above for Grade 2 Rash. 
3) If the rash recurs at Grade 2 or higher for a third time, the rash work up must be 
performed and the subject must be discontinued from the trial.  

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Table 5.2.1-1 
Guidelines for Treatment of Skin Rash 
Rash 
Grade 
Photographs 
Biopsy 
Medical 
Monitor 
or 
designee 
Consult 
Treatment 
Regimen 
KW-0761 
Study 
Participation 
Initial Drug Rash 
1 
Yes 
Required if 
topical 
steroids will 
be used 
Yes 
Topical 
corticosteroids 
as needed 
Continue 
Continue 
2 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Temporarily 
Stop; re-start 
if ≤ Grade1 
within 2 
weeks 
If rash does not 
resolve to ≤ Grade 
1 within 2 weeks 
consult with 
medical monitor 
3a 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Temporarily 
Stop: re-start 
if ≤ Grade 1 
within 2 
weeks  
If rash does not 
resolve to 
≤ Grade 1 within 
2 weeks consult 
with medical 
monitor 
Subsequent Drug Rash/Rechallenge 
1 
Yes 
Yes 
Yes 
Topical 
corticosteroids 
as needed 
Continue 
Continue 
2 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Temporarily 
Stop: re-start 
if ≤ Grade 1 
within 2 
weeks 
D/C if rash does 
not resolve to 
≤ Grade 1 within 
2 weeks 
3 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Discontinue 
Discontinue 
a Patients should be closely monitored for symptoms or signs that suggest SJS or TEN. If they occur, mogamulizumab 
should be interrupted and treatment should not restart unless SJS or TEN is ruled out and cutaneous reaction has resolved 
to Grade 1 or less. 
Subjects who require systemic steroid therapy to treat a severe skin rash including SJS/TEN 
should be discontinued from the study. 
5.2.2 
Study Drug: Vorinostat (ZOLINZA®) 
Treatment can be administered on an outpatient basis. Subjects will take 400 mg orally once 
daily with food.  

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Vorinostat is approved for marketing in the US, Japan and Australia and is indicated for the 
treatment of progressive, persistent or recurrent CTCL. Investigators will administer 
according to the currently approved US prescribing information (e.g. dosage and 
administration, warnings, precautions, adverse reactions, dose modifications and omissions 
and storage information). No other investigational or commercial agents or therapies other 
than the study treatments and those described in Section 5.4.1 may be administered with the 
intent to treat the subject’s malignancy. 
5.2.2.1 
Definition of Treatment Cycle 
Each treatment cycle is 28 days.  
5.2.2.2 
Delays in Dosing 
Refer to Section 5.2.2.5. 
5.2.2.3 
Duration of Treatment 
Subjects may remain in the treatment phase up until PD, drug intolerance or unacceptable 
toxicity, or until any of the other criteria for study removal are met, as defined in Section 5.5. 
Except in cases of unacceptable toxicity or drug intolerance, every effort should be made to 
ensure the subject remains in the study until disease progression (See Section 7.2.4, regarding 
definition of disease progression). 
At each cycle, the investigator must minimally have reviewed the mSWAT to determine if 
progression of skin disease has occurred prior to subsequent dosing. Ideally, results of flow 
cytometry and CT assessment, as applicable, should be reviewed at this visit as well. 
However, it is understood that these results may not be reported for several days and may not 
be available. Once those results are obtained evidence of progression in all compartments 
should be determined. 
In cases where the definition of PD or relapse is met but the clinical impression is 
questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after 
Year 1 if questionable finding in lymph nodes or viscera, with at least stable disease in other 
compartments) to avoid a subject being removed prematurely from the study. If PD is 
confirmed at this subsequent evaluation, subject should be discontinued from treatment. If PD 
is not confirmed at this subsequent evaluation, the subject may remain on study. 

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This course of action only applies to cases where the clinical impression is questionable; 
subjects in frank or obvious PD in any compartment should be discontinued from protocol 
therapy. 
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (CT, mSWAT, skin photographs and flow cytometry) should be done at that 
time to fully document disease progression. CT must be performed even if previously 
negative at baseline.  
If the subject experiences an overall CR, the subject may continue treatment for up to 
12 months or until progression, whichever comes first.  
For subjects who are continuing to receive study treatment at the time of the primary efficacy 
analysis, procedures and assessments are described in Section 7.7.   
5.2.2.4 
Replacement of Subjects 
Subjects will not be replaced.  
5.2.2.5 
Dose Modifications 
Management of severe or intolerable adverse reactions may require dose omission, reduction 
or interruption of vorinostat therapy. Refer to US prescribing information for complete 
recommendations regarding dose modifications. 
5.3 
Cross-over to Study Drug KW-0761 
Subjects who have received 2 full treatment cycles and demonstrate progression of disease on 
treatment with vorinostat at the 8 week (Cycle 2, Day 26-28) assessment, or anytime 
thereafter, may cross over to treatment with KW-0761 after discussion with Medical Monitor 
or designee and receipt of approval for cross over from KKD. Investigators should strive to 
maintain subjects on treatment for at least the 8 week period, adjusting the dose of vorinostat 
as needed for toxicities in order to allow sufficient time to see effect. In cases where a 
subject’s disease progresses rapidly (i.e., prior to 8 weeks), the Medical Monitor or designee 
should be contacted and may consider the possibility of early crossover, if appropriate for 
that subject. All subjects must undergo the full extent of disease evaluations (including CT 
scanning) to document PD prior to crossover.  
There must be at least 2 weeks between the last dose of vorinostat and first dose of KW-0761. 
Subject must continue to meet eligibility criteria outlined in Section 3.4 and all toxicity must 
have resolved to Grade ≤ 1 or to baseline in order to receive KW-0761. Treatment with 
KW-0761 should commence with procedures outlined for Day 1 in Table 1 of Study 

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Procedures for the first treatment cycle. In cases where a subject’s disease progresses rapidly, 
the Medical Monitor or designee should be contacted and may consider initiation of treatment 
with KW-0761 prior to the 2-week washout period. 
For subjects who are unable to tolerate the toxicities associated with vorinostat treatment, 
dose reduction should be initiated in an attempt to have the subject complete 2 full cycles of 
treatment. If the subject is unable to tolerate treatment with vorinostat despite attempts at 
dose reduction and has not had documented disease progression, the subject may receive 
KW-0761 after consultation with the Medical Monitor or designee and subsequent approval 
documentation from the Sponsor.  
Drug intolerance is defined as: 
• 
A serious AE attributed to the drug; 
• 
≥ Grade 3 AEs excluding inadequately treated nausea, vomiting and diarrhea and 
alopecia. 
5.4 
Concomitant Therapy 
Subjects should receive appropriate medical care for all intercurrent medical conditions 
consistent with community standards of medical care. Subjects are to receive vigorous 
supportive care for study medication-related toxicities and appropriate palliation for tumor 
symptoms, such as pain and anorexia.  
All concomitant treatments whether for treatment of concurrent medical conditions, toxicity, 
management of pain, infections or other complications of the malignancy, must be recorded 
on the relevant electronic case report form (eCRF) page along with the reason for use. 
Medication taken within 30 days prior to the first dose of study drug, and at any time after the 
start of treatment until 30 days after the final study drug administration will be recorded. A 
medication taken during follow-up will also be recorded if it is used to treat an AE or is 
temporally associated with an AE and may have a causal relationship. 
While on study treatment, subjects are not permitted to receive any experimental therapy or 
anticancer therapy other than the study medication. Any subject requiring other anticancer 
therapy is to be removed from study treatment.  
5.4.1 
Permitted Treatment 
• 
Hematopoietic growth factors and erythropoiesis-stimulating agents (based on threshold 
and target hemoglobin levels in the American Society of Hematology (ASH)/American 
Society of Clinical Oncology (ASCO) guidelines) (Rizzo, 2010) are allowed, if consistent 
with regional approved prescribing information, after completing Cycle 1. 

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• 
Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone 
equivalent) for at least 4 weeks prior to the Pre-treatment Visit may continue use. 
Subjects may receive intra-articular corticosteroid injections, intraocular corticosteroids 
drops, inhalation or nasal corticosteroids and replacement doses of systemic 
corticosteroids as needed. 
• 
Subjects on a stable dose of medium or low potency topical corticosteroids for at least 
4 weeks prior to the Pre-treatment Visit may continue use at the same dose, although the 
investigator should attempt to taper the use to the lowest dosage tolerable while on study. 
• 
Prophylactic treatment for the infectious complications of T-cell lymphoma is permitted 
at the discretion of the investigator. 
• 
For subjects receiving vorinostat, prolongation of prothrombin time (PT) and 
International Normalized Ratio (INR) have been observed in subject receiving 
concomitant therapy with coumarin-derivative anticoagulants, carefully monitor PT and 
INR in these subjects. 
• 
Influenza vaccination consisting of killed virus or viral particles may be administered to 
subjects on study. Subjects should not receive an influenza vaccine containing live 
attenuated virus. It should also be understood that because KW-0761, as well as CTCL, 
can affect the immune system, immunity to influenza may not be achieved despite 
vaccination. 
5.4.2 
Prohibited Treatment 
• 
Initiation of treatment with systemic steroids or increase in dose while on study is not 
permitted except to treat an infusion reaction (see Section 5.2.1.7). Subjects who require 
systemic steroid therapy to treat a severe skin rash should be discontinued from the study 
(see Section 5.2.1.8). 
• 
Initiation of treatment with topical corticosteroids while on study is not permitted except 
to treat an acute rash. 
• 
Any experimental therapy or anticancer therapy including radiation and phototherapy 
other than the study medications. 
• 
Any live or live attenuated vaccine. 
• 
Alternative medicines, particularly use of St. John’s Wort. 
• 
Immunomodulatory agents such as methotrexate; azathioprine; iv immunoglobulin; 
cyclophosphamide; cyclosporine; mycophenolate; infliximab; etanercept; leflunomide; 
adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-α; interferon-β; 
IL-2 and natalizumab.  
• 
Other concurrent HDAC inhibitors including valproic acid. 
• 
Whenever possible, concomitant use of drugs which may cause a prolongation of the QTc 
interval should be avoided. If such a drug is necessary (e.g., anti-emetics), monitor the 
QTc interval closely. 

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5.5 
Criteria for Removal from Study 
In the absence of a medical contraindication or significant protocol violation, every effort will 
be made by the Principal Investigator to keep the subject in the study. However, should the 
subject decide to discontinue treatment, all efforts will be made to complete and report the 
observations as thoroughly as possible, including a complete final evaluation at the time of 
the subject’s withdrawal with an explanation of why the subject is withdrawing from the 
study. 
Study treatment will be stopped if any of the following events occur:  
• 
Disease progression (as defined in Section 7.2.4); 
• 
An infusion-related reaction (see Section 5.2.1.7);  
– with a severity of ≥ Grade 2 upon re-challenge with KW-0761, 
– with a severity of Grade 3 with symptoms that do not abate after 30 minutes, 
– with a severity of Grade 4, 
– requiring the administration of systemic vasopressors, 
– that results in hospitalization (directly due to infusion reaction symptoms), 
• 
Initiation of treatment with systemic corticosteroids, except when initiated to treat an 
infusion reaction (see Section 5.2.1.7); 
• 
A true hypersensitivity (i.e., allergic) reaction to KW-0761 with a severity of ≥ Grade 2; 
• 
A rash which recurs and becomes Grade 3 on re-challenge (see Section 5.2.1.8); 
• 
A rash which recurs at Grade 2 or higher for a third time on re-challenge (see Section 
5.2.1.8); 
• 
A rash which requires systemic steroid therapy (see Section 5.2.1.8); 
• 
Confirmed SJS/TEN (see Section 5.2.1.8); 
• 
The subject has any clinical AE, laboratory abnormality, intercurrent illness, or other 
medical condition that indicates to the Investigator that continued participation is not in 
the best interest of the subject. The Investigator should make a distinction between AEs 
that may require only interruption of study medication and those that require 
discontinuation; 
• 
The subject wishes to withdraw consent from the study in the absence of a medical need 
to withdraw as determined by the Investigator; 
• 
The Investigator concludes that it is in the best interest of the subject to discontinue study 
treatment including subjects who have not benefited from treatment; 
• 
Subject is willingly or inadvertently noncompliant in the opinion of the Investigator; 
• 
Administrative reasons determined by the Sponsor; or 
• 
If pregnancy is suspected while the subject is receiving study treatment, the study 
medication must immediately be withheld until the result of pregnancy testing is known. 

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If pregnancy is confirmed, the study medication will be permanently discontinued and the 
subject withdrawn from treatment. 
In the case of pregnancy that occurs while the subject is receiving study medication through 
6 months after the last dose of study medication, the Investigator must immediately notify the 
Sponsor of this event and record the pregnancy on the Pregnancy Surveillance Form. The 
Sponsor must also be notified if a partner of a study subject becomes pregnant while the 
subject was receiving study medication through 6 months after the last dose of study 
medication. Reasonable attempts will be made to follow the pregnancy to conclusion in order 
to obtain information regarding the outcome. 
The Investigator must complete all applicable End-of-treatment visit procedures (i.e., safety 
laboratory parameters, electrocardiogram (ECG), physical examination, vital signs) and 
eCRF pages for subjects who discontinue treatment, and include the reason for 
discontinuation of treatment.  
6 
STUDY PROCEDURES 
The key study procedures and the frequency of their occurrences are outlined in the Study 
Procedures Tables (Table 1, Table 2, and Table 3). Labs, ECG, and physical exams on day of 
treatment should be obtained prior to study treatment.  
For subjects who are continuing to receive study treatment at the time of the primary efficacy 
analysis, procedures and assessments are described in Section 7.7. Procedures to be followed 
for subjects who are ongoing in the study (i.e., subjects who are continuing to receive 
KW-0761 or who are in safety or survival follow-up) at the time of initial marketing 
authorization are described in Section 7.8.  
7 
STUDY MEASUREMENTS 
Screening evaluations used to determine the subject’s study eligibility must be completed 
within 30 days prior to starting treatment unless otherwise specified. 
Written informed consent must be obtained prior to any study-specific procedures. 
Results of all screening evaluations must be reviewed by the Investigator or his/her designee 
to ensure that all eligibility criteria have been satisfied prior to registering the subject with the 
Sponsor. All pathology reports relevant to confirmation of the diagnosis of CTCL (mycosis 
fungoides or Sezary syndrome) for all enrolled subjects should be de-identified and provided 
to the Sponsor. For subjects with SS, this would include results confirming fulfillment of B2 
criteria including a clone in the blood that matches that of the skin per Section 3.2.  

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An End-of-treatment visit must be conducted for all subjects who discontinue from study 
treatment. This visit must occur within 30 days after the last dose of study medication. All 
End-of-treatment assessments must be conducted prior to the initiation of new therapy. 
7.1 
Safety Evaluations 
The safety of KW-0761 and vorinostat will be determined by reported AEs, changes in 
physical examinations, vital sign measurements, ECGs and laboratory analyses. Safety 
evaluations will be performed throughout the study. All subjects who received at least one 
dose, including a partial dose, of study drug will be evaluated for safety. The NCI-CTCAE 
v4.0 system will be used to grade AEs, both clinical and laboratory. AEs will be grouped and 
tabulated by Medical Dictionary for Regulatory Activities (MedDRA) preferred terms by 
system organ class. All subjects will be assessed regularly for potential occurrence of AEs 
from the time of signing the informed consent until 90 days after the last dose or initiation of 
alternative therapy whichever comes first. In all subjects who cross over from vorinostat to 
KW-0761, the causality of any reported AEs should be assessed for both drugs for 30 days 
after vorinostat was stopped (or later if the event is considered to be related to vorinostat).   
7.1.1 
Clinical Laboratory Evaluations 
Clinical laboratory assessments will be performed at the visits specified in the Study 
Procedures. A pregnancy test (serum or urine) is to be performed for all women of 
childbearing potential prior to administration of study medication.  
Any clinically important abnormal laboratory values noted at the screening visit will be 
recorded as medical history. In addition, in order for KKD to collect additional information 
about clinically important laboratory abnormalities, at minimum, the following laboratory 
abnormalities should be captured on the non-serious or serious AE pages of the eCRF as 
appropriate: 
• 
Any laboratory test result that meets the criteria for a SAE; 
• 
Any laboratory abnormality that requires the subject to have study medication 
discontinued or interrupted; 
• 
Any laboratory abnormality that requires the subject to receive specific corrective 
therapy. 
All clinically important abnormal laboratory tests occurring during the study will be repeated 
at appropriate intervals until (1) the value returns to baseline, (2) the value is judged to be 
clinically acceptable by the Investigator and the Sponsor, or (3) a diagnosis that explains the 

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abnormal laboratory value is made. When possible, the Investigator should report the clinical 
rather than the laboratory term (e.g., anemia versus low hemoglobin). 
Clinical laboratory assessments will include the following: 

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Table 7.1.1-1 
Clinical Laboratory Assessments 
Serum Chemistry 
Sodium 
Albumin 
Calcium 
Potassium 
SGPT (ALT) 
Phosphorus  
Glucose 
SGOT (AST) 
Chloride 
Blood urea nitrogen 
(BUN) 
Alkaline phosphatase 
Bicarbonate (serum or blood) 
Creatinine 
Total bilirubin 
Uric acid 
Total protein 
Lactate dehydrogenase 
(LDH) 
Magnesium 
Thyroid function 
T4 (free) 
TSH 
Coagulation Panel 
International normalized ratio (INR) 
Partial thromboplastin time 
(PTT) or 
Activated Partial 
thromboplastin time (aPTT) 
Hematology  
Complete blood count 
(CBC) and 
differential 
Platelet count 
Absolute neutrophil 
count 
 
T-cell counts 
Absolute CD4 count 
Absolute CD8 count 
CD4 and CD8 counts will be reported based on the flow cytometric sample sent to 
Quest while the subject is on study. On site counts need only be obtained at End-of-
treatment visit with appropriate follow up if less than 200/mm3. 
Urinalysis 
routine urinalysis or dipstick measurements and, if clinically indicated, microscopic 
analysis. Parameters should include: 
Color 
WBC 
 
Specific Gravity 
RBC or hemoglobin 
 
pH 
Protein 
 
Glucose 
Ketones 
Pregnancy Test 
A serum or urine pregnancy test will be performed for all women of childbearing 
potential at screening.  
Virus Testing 
hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis 
C antibodies (HC Ab) 
HIV  
HTLV-1 
7.1.2 
Vital Signs and Body Weight 
Vital signs (pulse, respiration rate, temperature, and blood pressure) will be measured, with 
the subject in the seated position, at the visits specified in the Study Procedures (Table 1, 
Table 2, and Table 3). Additional vital signs will be obtained if clinically significant signs or 
symptoms occur. 

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Weight will be included in vital sign assessments. The subject’s height will be measured at 
the Pre-Treatment visit.  
7.1.3 
Physical Examination 
The Investigator will perform a full physical examination at the Pre-treatment (including 
height at only this visit) and End-of-treatment visits and brief physical examinations at other 
visits specified in the Study Procedures (Table 1, Table 2, and Table 3). The full physical 
examination requires assessment of the following categories:  head, eyes, ears, nose, and 
throat (HEENT), heart, lungs, abdomen, skin, musculoskeletal, extremities, neurological, 
lymph nodes and ‘other.’ Brief physical examination consists of examination of pertinent 
systems, i.e., those in which abnormalities were noted previously as well as those likely to be 
affected during the course of therapy and those suggested by reported adverse experiences.  
Attention should be paid to those body systems referable to possible autoimmune disorders, 
such as the joints, the eyes, the GI tract as well as signs and symptoms of hypothyroidism. To 
assist in this surveillance, a list of directed questions and suggested actions is provided in 
Appendix 4. 
ECOG Performance Status (PS) will be assessed at each exam according to the ECOG PS 
criteria (Appendix 2). 
7.1.4 
Electrocardiograms 
A baseline 12-lead ECG is to be obtained at the Pre-treatment Visit. Follow up ECGs should 
be performed during the study if clinically indicated and then at the End of Treatment visit. 
The Investigator will have the responsibility for evaluating the ECG interpretation in 
relationship to clinical signs and symptoms and for reaching a medical decision regarding the 
subject’s medical status. If not within normal limits, the ECG findings should be marked 
“clinically significant” or “not clinically significant” (i.e., “CS” or “NCS”) and the ECG 
should be initialed and dated by the Investigator.  
7.1.5 
Blood Sample for Determination of Natural Ligands 
Blood samples will be drawn to measure the concentration of natural ligands such as 
CCL17/TARC and CCL22/MDC at the visits specified in the Study Procedures. Analysis of 
samples will be performed by a central laboratory designated by the Sponsor. Instructions for 
preparation and shipment of samples will be provided in the Laboratory Manual. (As of 

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Amendment 10, central laboratory analysis of samples will no longer be performed [see 
Section 7.8].) 
7.1.6 
Genomic Sampling (For subjects receiving KW-0761 as first assigned 
therapy only) 
A saliva sample will be collected to obtain baseline germline DNA sample to assess 
Fc-gamma receptor polymorphisms. Exploratory analysis of the effect of this genetic 
determinant on safety parameters may be performed. 
Analysis will be performed by a central laboratory designated by the Sponsor. Instructions for 
preparation and shipment of samples will be provided in the Laboratory Manual. 
7.1.7 
Immunogenicity (For subjects receiving KW-0761) 
Serum samples will be drawn for the determination of anti-KW-0761 antibodies and 
concentration of KW-0761 at the visits specified in the Study Procedures. Analysis of 
samples will be performed by a central laboratory designated by the Sponsor. Instructions for 
preparation and shipment of samples will be provided in the Laboratory Manual. (As of 
Amendment 10, central laboratory analysis of samples will no longer be performed [see 
Section 7.8].) 
7.2 
Efficacy Evaluations 
Response in skin and blood will be evaluated every 4 weeks during treatment. In the first year 
of treatment, response in lymph nodes and viscera will be documented at 4 weeks after the 
start of study treatment (end of Cycle 1) and every 8 weeks thereafter. After the first year, 
response in the lymph nodes and viscera will be documented every 16 weeks. In the first year 
of treatment, the global composite response (including skin, blood, lymph nodes and viscera) 
will be assessed at 4 weeks (end of Cycle 1) and every 8 weeks thereafter (Cycle 3, 5, etc.); 
after the first year, global composite response will be assessed every 16 weeks (Cycle 17, 21, 
etc.).   
For those subjects who cross over from the vorinostat arm to KW-0761 treatment, response 
within the second arm of the study will be measured from the first day of dosing with 
KW-0761. Baseline measurements for this arm are considered to be those taken at the last 
assessment which documented progression on vorinostat or if repeated, assessment 
completed closest to and before the first KW-0761 infusion (i.e., mSWAT done on Cycle 1, 
Day 1 is the new baseline). 

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Prior to starting study treatment, visual inspection of the skin with photographs and 
measurements (mSWAT), assessment of CT images and hematological examinations will be 
done to document extent of disease. Skin disease will be evaluated using a modification of 
the SWAT (Olsen, 2007; Stevens, 2002). Response for skin will be based on mSWAT scores. 
In addition, pruritus will be evaluated using a Likert scale and Itchy QoL. Lymph nodes and 
visceral disease will be evaluated by CT. The response in blood will be assessed by flow 
cytometry. 
The response in all compartments (skin, blood, lymph nodes and viscera, as applicable) and 
overall response will be assessed, except as otherwise noted, in accordance with the response 
criteria determined by consensus of the International Society of Cutaneous Lymphomas 
(ISCL), the United States Cutaneous Lymphoma Consortium (USCLC) and the Cutaneous 
Lymphoma Task Force of the European Organization for Research and Treatment of Cancer 
(EORTC) (Olsen, 2011).  
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (CT, mSWAT, skin photographs and flow cytometry) should be done at that 
time to fully document disease progression. CT must be performed even if previously 
negative at baseline. 
7.2.1 
Evaluation of Skin Disease 
7.2.1.1 
Skin Biopsy 
7.2.1.1.1 CCR4 Expression 
A skin biopsy will be taken at baseline for determination of CCR4 expression by IHC. In the 
event it is not possible to obtain a skin biopsy, use of an archived sample (taken within 
6 months prior to treatment) may be allowed with prior authorization from the Sponsor. To 
determine if vorinostat alters CCR4 expression, investigators are strongly encouraged to 
obtain an additional skin biopsy for the determination of CCR4 expression, prior to treatment 
with KW-0761, in subjects who cross over from treatment with vorinostat.  
Tissue is typically expected to have been prepared for standard histopathological examination 
following formalin or other fixation and embedding in paraffin. The paraffin block is to be 
submitted to a Central Laboratory designated by the Sponsor. If the study site is unable to 
process the tissue, a fresh sample may be sent to the Central Laboratory on the day obtained. 
Submission of unstained slides, while not recommended due to stability concerns with the 
sample, will be accepted. Specific instructions for sample preparation and handling will be 
provided in the Laboratory Manual. 

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With the consent of the subject, the remainder of the skin or lymph node biopsy specimens, 
i.e., the tissue that is left over after the study-specific tests are conducted, will be archived 
and the remainders of the specimens will be used in the development of an 
immunohistochemical assay for the semi-quantitative detection of CCR4. All specimens 
submitted for the purpose of the development of this assay should be managed by the 
investigator and his/her staff with adequate precautions to ensure subject confidentiality, in 
accordance with applicable national and/or local laws and regulations on personal data 
protection. 
7.2.1.1.2 Disease Status/Other Biopsy Recommendations 
Subjects with clinical features suggestive of LCT must have a biopsy performed within 
4 months prior to Cycle 1 Day 1 to rule out transformed disease. 
Skin biopsies at the end of the cycle and to confirm a CR are optional and can be performed 
at the discretion of the investigator. Analysis of these biopsies will be done by the pathologist 
at the study site. 
Additional translational assessments may be performed to further characterize the response in 
skin on any biopsy samples obtained. 
7.2.1.2 
Skin Photographs 
Cameras will be supplied to the study site by Canfield Scientific, Inc. for use in this study. 
All involved areas that are representative of the subject’s extent of disease, will be selected at 
baseline and measured and photographed using the digital camera provided by Canfield. In 
addition, half-body global photos (waist to feet, waist to top of head and sides) will also be 
obtained. Photos should be taken against a blue backdrop.  
Skin photographs should be obtained prior to administration of study drug on Day 1 of the 
first treatment cycle and then as specified in the Study Procedures tables.  
Special care should be taken to shield the subject’s identity in accordance with local 
guidelines on data privacy.  
Photos must be labeled with only the subject identification number and initials. Digital photos 
will then be submitted on an ongoing basis to Canfield Scientific, Inc. for quality review. 
Canfield Scientific, Inc. will review photographs on an ongoing basis for assessment of 
image quality and provide feedback to sites to ensure the photographs are appropriately 
representative of extent of skin disease. (As of Amendment 8, submission of photographs to 
Canfield Scientific, Inc. is no longer required.) 

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More detailed instructions regarding photographing of skin lesions will be provided in the 
Photography User Manual. 
7.2.1.3 
Modified Severity Weighted Assessment Tool (mSWAT) 
Skin lesions and erythema will be evaluated using the mSWAT.  
The mSWAT is an objective, quantitative, severity-weighted method to assess the extent of 
skin lesions. An mSWAT score is derived by measuring each lesion as a percentage of total 
body surface area (%TBSA) and multiplying it by a severity-weighting factor (1 = patch, 
2 = plaque, 4 = tumor). All individual numbers are then added to produce a total score.  
Areas of skin involvement identified as patch, plaque, or tumor and erythema are defined in 
Table 7.2.1-1 and Table 7.2.1-2: 
Table 7.2.1-1 
Modified Severity Weighted Assessment Tool 
Skin Lesion Definitions 
Lesion Type 
Abnormal Skin 
Erythema 
Patch 
Abnormal skin not elevated from 
normal skin 
Flat erythema or erythema with mild 
infiltration 
Plaque 
Abnormal skin elevated from normal 
skin by < 5 mm 
Elevated erythema or erythema with moderate 
infiltration 
Tumor 
Abnormal skin elevated from normal 
skin by ≥ 5 mm 
Erythema with fissuring, ulceration, or tumor 
mSWAT Score Calculation 
Sum of %TBSA from all body regions affected by patches x severity-weighting factor of 1  
+ Sum of %TBSA from all body regions affected by plaques x severity-weighting factor of 2  
+ Sum of %TBSA from all body regions affected by tumors x severity-weighting factor of 4 
= Total mSWAT (maximum score = 400). 
 
 

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Table 7.2.1-2 
Modified Severity Weighted Assessment Tool Score 
Body region (%BSA) 
Patch* 
Plaque* 
Tumor* 
      Head (7 %) 
 
 
 
      Neck (2%) 
 
 
 
      Anterior trunk (13%) 
 
 
 
      Arms (8%) 
 
 
 
      Forearms (6%) 
 
 
 
      Hands (5%) 
 
 
 
      Posterior trunk (13%) 
 
 
 
      Buttocks (5%) 
 
 
 
      Thighs (19%) 
 
 
 
      Legs (14%) 
 
 
 
      Feet (7%) 
 
 
 
      Groin (1%) 
 
 
 
Subtotal of lesion BSA 
 
 
 
Weighting factor 
x1 
x2 
x4 
Subtotal lesion BSA x weighting factor 
 
 
 
mSWAT score = summation of each column line above =  
patch = any size lesion without induration or significant elevation above the surrounding uninvolved skin: poikiloderma may 
be present.  
plaque = any size lesion that is elevated or indurated; crusting, ulceration or poikiloderma may be present.  
tumor = any solid or nodular lesion ≥ 1 cm in diameter with evidence of deep infiltration in the skin and/or vertical growth.  
 
7.2.1.4 
Response Criteria for Skin 
Response in skin will be determined by changes in mSWAT score as specified in Table 
7.2.1-3. Responses (CR and PR) must be confirmed for a minimum of 4 weeks. 

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Table 7.2.1-3 
Response Criteria for Skin, as assessed by mSWAT scoresa 
Response 
Definition 
CR 
100% clearance of skin lesionsb  
PR 
50 to 99% clearance of skin disease from baseline without new tumors (T3) in subjects with T1, 
T2 or T4 only skin disease 
SD 
< 25% increase to <50% clearance in skin disease from baseline without new tumors (T3) in 
subjects with T1, T2 or T4 only skin disease 
PDc 
(1) ≥ 25% increase in skin disease from baseline or 
(2) New tumors (T3) in subjects with T1, T2 or T4 only skin disease or 
(3) Loss of response:  in those with CR or PR, increase of skin score of greater than the sum of 
nadir plus 50% baseline score 
Relapsed 
Any disease recurrence in those with CR  
a: Based on mSWAT score. 
b: A biopsy of normal appearing skin is unnecessary to assign a CR. However, a skin biopsy should be performed of a 
representative area of the skin if there is any question of residual disease where otherwise a CR would exist. If histologic 
features are suspicious or suggestive of MF/SS (see histologic criteria for early MF7), the response should be considered 
a PR only. 
c: Whichever criterion occurs first. 
d: For purposes of the study, relapse should be defined as loss of response (as defined for PD) in those with CR, ie, increase 
of skin score of greater than the sum of nadir plus 50% baseline score. Subjects may remain on treatment until subsequent 
measurement to confirm progression. 
 
7.2.1.5 
Pruritus Evaluation 
The extent of pruritus can have a significant impact on the subject’s QoL. A Likert scale 
(Appendix 9) will be completed by each subject to assess their degree of pruritus at the visits 
specified in the Study Procedures. The Itchy Quality of Life questionnaire (Desai, 2008) (see 
Appendix 5) will also be completed at these visits to further evaluate the impact of pruritus 
on their QoL. Medications taken to treat pruritus will be documented. 
7.2.2 
Evaluation of Blood Disease 
7.2.2.1 
Flow Cytometric Analysis 
A peripheral blood sample will be used to evaluate circulating malignant T-cells and further 
assess immune cells in the blood.  
Samples will be sent to a central laboratory designated by the Sponsor. Specific directions for 
sample preparation and packaging will be provided in the Laboratory Manual. (As of 
Amendment 10, central laboratory analysis of samples will no longer be performed [see 
Section 7.8].) 

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7.2.2.2 
Response Criteria in Blood 
In subjects with blood involvement, all blood  responses (CR and PR) must be confirmed for 
a minimum of 4 weeks.  
Response criteria are specified in Table 7.2.2-1. 
Table 7.2.2-1 
Blood Response Criteriaa 
CRb 
B0 
PRc 
> 50% decrease in quantitative measurements of blood tumor burden from baseline in those with 
high tumor burden at baseline (B2)  
SD 
Fails to attain criteria for CR, PR or PD 
PDd 
(1) B0 to B2 or  
(2) > 50% increase from baseline and at least 5,000 neoplastic cells/μL or 
(3) Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from 
nadir and at least 5,000 neoplastic cells/μL 
Relapse 
Increase of neoplastic blood lymphocytes to ≥ B1 in those with CR 
a: As determined by absolute numbers of neoplastic cells/uL. 
b: If a bone marrow biopsy was performed at baseline and determined to unequivocally be indicative of lymphomatous 
involvement, then to confirm a global CR where blood assessment now meets criteria for B0, a repeat bone marrow 
biopsy must show no residual disease or the response should be considered a PR only.  
c: There is no PR in those with B1 disease at baseline as the difference within the range of neoplastic cells that define B1 is 
not considered significant and should not affect determination of global objective response. 
d: Whichever occurs first. 
 
7.2.3 
Evaluation of Disease in Lymph Nodes and Viscera 
7.2.3.1 
Baseline Tumor Assessments 
The baseline tumor burden will be assessed by CT of the neck, chest, abdomen and pelvis 
within 30 days prior to the first dose of study drug. The Investigator will identify, 
prospectively, the lesions to be followed to evaluate the subject’s response to therapy. Lymph 
nodes must be > 15 mm in the long axis (greatest transverse diameter, GTD) or > 10 mm in 
the short axis if the GTD is > 10 to ≤ 15 mm. 
Lymph node biopsies may be performed, at the discretion of the Investigator, to rule out 
inflammation or to confirm disease. Analysis of these biopsies will be done by the pathologist 
at the study site. 
7.2.3.2 
Method of Tumor Response Assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at Screening and at reassessment during treatment. 
Imaging-based evaluation is preferred to evaluation by clinical examination when both 

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methods have been used to assess the anti-tumor effect of a treatment. Lesions evaluated 
clinically will only be considered measurable when they are superficial (e.g., skin nodules, 
palpable lymph nodes). In the case of skin lesions, documentation by color photography, 
including a ruler to estimate the size of the lesion, is recommended. Contrast enhanced CT 
will be considered the best currently available and reproducible method to measure target 
lesions selected for response assessment. For subjects who are allergic to contrast agents, 
non-contrast CT can be performed. The allergy must be documented on the Medical History 
eCRF. Ultrasound is not an acceptable method to measure disease. Central review of 
radiology may be performed to confirm the date of disease progression. Images should be 
transmitted to the central radiology group as described in the Imaging Manual. 
7.2.3.3 
Determination of Response in Lymph Nodes and Viscera 
The Investigator will make a determination of response based on criteria as specified in Table 
7.2.3-1 and Table 7.2.3-2. In subjects with lymph node and/or visceral involvement, 
responses (CR and PR) must be confirmed for a minimum of 4 weeks. 

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Table 7.2.3-1 
Response in Lymph Nodesa 
CR 
All lymph nodes are now ≤ 15 mm in GTD by the method used to assess lymph nodes at baseline. 
In addition, lymph nodes that were ≤ 15 mm in GTD and > 10 mm in the short axis at baseline 
must now be ≤ 10 mm in the short axis. 
PR 
Cumulative reduction ≥ 50% of the SPD as compared to baseline and no new lymph node 
(> 15 mm in the GTD or > 10 mm in the short axis if the GTD is > 10 mm to ≤ 15 mm).  
SD 
Fails to attain the criteria for CR, PR, or PD 
PD 
Must meet any of the following: 
(1) ≥ 50% increase in SPD from baseline of lymph nodes, or 
(2) Loss of response, which is > 50% increase from nadir SPD of lymph nodes in subjects 
previously assessed as PR, or 
(3) > 50% increase compared to nadir, but which does not meet the criteria for PR (i.e., up to a 
50% reduction compared to baseline), or 
(4) Any new nodal lesion > 15 mm in the GTD or >10 mm in short axis diameter if the GTD is  
> 10 mm to ≤ 15 mm) 
Relapse 
(1) Any new lymph node > 15 mm in GTD or >10 mm in short axis if the GTD is > 10 mm to 
≤ 15 mm 
(2) Recurrence of any lymph node previously selected at baseline, which was previously assessed 
as a CR, but which has recurred and measures  > 15 mm in the GTD or > 10 mm in the short axis 
if the GTD is > 10 mm to ≤ 15 mm. 
Unable to 
Evaluate 
A lymph node present at baseline, but which was not measured or which subsequently became 
unevaluable, leading to an inability to determine the status of that particular node for the time 
point in question. 
a: Peripheral and central lymph nodes 
GTD=greatest transverse diameter; SPD=sum of the products of the diameters 
 
 

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Table 7.2.3-2 
Response in Viscera 
CR 
(1) 100% reduction in the SPD of all lesions selected at baseline. 
(2) Liver or spleen or any organ considered involved at baseline should be considered normal by 
imaging. 
(3) No nodules should be present on any imaging of liver or spleen. 
PR 
(1) ≥ 50% regression in all splenic or liver nodules, or in measurable disease (SPD) in all organs 
abnormal at baseline.  
(2) No increase in the size of liver or spleen consistent with disease progression and no new sites of 
involvement.  
SD 
Fails to attain the criteria for CR, PR, or PD 
PD 
Must meet any of the following: 
(1) > 50% increase in SPD of organs involved at baseline, or 
(2) New organ involvement, or 
(3) Loss of response, which is > 50% increase from nadir in the SPD of previous organ involvement 
in subjects previously assessed as PR, or 
(4) > 50% increase compared to nadir, but which does not meet the criteria for PR (i.e., up to a 50% 
reduction compared to baseline). 
Relapse 
(1) New organ involvement in subjects previously assessed as CR. 
(2) Recurrence of any lesion previously selected at baseline, which was previously assessed as a CR, 
but which has recurred and meets the measurement criteria (≥ 10 mm and/or 2× the reconstruction 
interval in the GTD). 
Unable 
to 
Evaluate 
An area of visceral disease present at baseline, but which was not measured or which subsequently 
became unevaluable, leading to an inability to determine the status of that particular area for the time 
point in question. 
GTD=greatest transverse diameter; SPD=sum of the products of the diameters 
 
7.2.4 
Global Composite Response Score 
Overall response will be based on response in each compartment (skin, blood, lymph nodes 
and viscera) as specified in Table 7.2.4-1.  

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Table 7.2.4-1 
Global Composite Scoring System 
Global 
Score 
Definition 
Skin 
Nodes 
Viscera 
Blood 
CR 
Complete disappearance of all 
clinical evidence of disease 
CR 
All categories have CR/NI 
PR 
Regression of measurable 
disease 
CR 
All categories do not have a CR/NI and no 
category has a PD  
PR 
No category has a PD and if any other category 
involved at baseline, at least one has a CR or 
PR  
SD 
Failure to attain CR, PR or PD 
PR 
No category has a PD and if any other category 
involved at baseline, no CR or PR in any 
SD 
CR/NI,PR,SD in any category and no category 
has a PD  
PD 
Progressive disease 
PD in any category 
Relapse 
Recurrence of disease in prior 
CR 
Relapse in any category  
NI=non-involved 
 
Node, viscera and blood response contributes towards global response only if disease present 
at baseline, unless defining global PD which is met by new disease in previously uninvolved 
compartment.  However, subjects who meet PD criteria in any compartment, or relapse in 
blood, lymph nodes or viscera, confirmed at 2 consecutive visits must be discontinued from 
study treatment due to disease progression/relapse. If subsequent assessment does not 
confirm PD in any compartment, or relapse in blood, lymph nodes or viscera, subject may 
continue on treatment. An unconfirmed PD/relapse would not preclude future responses (CR 
or PR). 
If PD is documented in any compartment at any point leading to subject’s discontinuation 
from treatment, the overall global composite score should be completed at that time even if 
all compartments have not been assessed. 
7.2.4.1 
Independent Review of Progression 
A blinded independent review of response data for each subject will be performed to make a 
determination regarding progression and the date of progression. The nodal and visceral 
compartments evaluation will be based upon radiologic data. The independent radiology 
review of radiographic exams will provide an assessment of tumor response and progression 
for all subjects. A separate radiology charter will detail the roles and responsibilities of the 
radiology reviewers and how the reads will be performed. An independent reviewer (IR) will 
assess PFS based on date of progression or death, whichever comes first. For this assessment 

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the independent reviewer will be supplied the results of the independent radiology review, the 
mSWAT score for each subject, as assessed by the investigator, and the results of central 
flow cytometry in order to assess blood response, and date of death for subjects who died 
before progression.  
Secondarily, the IR will review the date of any objective responses (CR or PR).  
7.3 
Pharmacokinetics (for subjects receiving KW-0761) 
Serum samples will be drawn in subjects who receive KW-0761 (as first assigned therapy or 
crossover) at the timepoints specified in the Study Procedures Tables (Table 1, Table 2, and 
Table 3) for determination of KW-0761 concentration, through Cycle 3 and at the 
End-of-treatment Visit. At selected sites, 4 additional samples will be drawn between 6 and 
8 hours, and at 24, 48, and 72 - 96 hours after the first infusion on Day 1/Cycle 1 in 
approximately 10 subjects, including crossover subjects. Blood samples obtained 
post-infusion should be obtained from the arm contralateral to that of study drug 
administration. The exact time of sample draw must be recorded in the eCRF.  
All samples will be sent to a central laboratory designated by the Sponsor. Specific directions 
for sample preparation and packaging will be provided in the Laboratory Manual. 
7.4 
Quality of Life Assessments 
Subjects with CTCL often suffer from the symptoms related to their disease (pain, sleep 
disturbance, etc.), the social and psychological problems related to sometimes unsightly skin 
lesions and the burden of living with a chronic disease. In an effort to assess some of these 
QoL issues, the Skindex-29 (see Appendix 6), FACT-G (see Appendix 7) and EQ-5D-3L (see 
Appendix 8) will be administered. 
7.5 
Follow-Up 
All subjects will be contacted by telephone every 30 days (± 7 days) up to 90 days after the 
last dose of study medication or initiation of alternative therapy, whichever comes first, to 
confirm any new onset AEs or toxicities. If a subject who has received KW-0761 undergoes a 
stem cell transplant at any time during or after the 90-day follow-up period, AEs/SAEs 
should be documented from the transplant procedure through 180 days post-transplant.  
During follow-up, medications used to treat an AE and those that are temporally associated 
with the AE and may have a causal relationship will be recorded. In all subjects who cross 

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over from vorinostat to KW-0761, the causality should be assessed for both drugs for 30 days 
after vorinostat was stopped (or later if the event is considered to be related to vorinostat).  
• 
After a subject who receives KW-0761 goes off study, if CD4 and CD8 counts are less 
than 200/mm3 at the End-of-treatment visit, they will be followed every 3 months 
(± 14 days) until they return to at least 200/mm3, initiation of alternative therapy or 
1 year, whichever comes first. 
• 
In the absence of disease progression, all subjects or their referring physicians will be 
contacted every 3 months (± 14 days) until documented disease progression or death, or 
initiation of alternative therapy. 
• 
All subjects or their referring physician will be contacted every 3 months (± 14 days) to 
ascertain survival status.  
• 
For all subjects who have received KW-0761, subsequent stem cell transplant information 
should be recorded in a separate CRF provided by the Sponsor. For subjects who undergo 
transplant, concomitant medications and AEs/SAEs should be documented through 
180 days post-transplant on the CRFs provided. 
• 
All follow up information and attempts to obtain follow up information should be 
documented in the subject’s source record. 
7.6 
Follow-Up for Subjects Achieving a Complete Response 
Those subjects who do not continue treatment after achieving a CR will undergo the 
following assessments every 8 weeks (± 14 days) for the first 6 months (if CR achieved prior 
to one year on study) and then every 16 weeks (± 14 days) thereafter until progression: 
• 
Chemistry/Hematology profile;  
• 
Skin photographs; 
• 
mSWAT; 
• 
Pruritus evaluation; 
• 
Blood sample for flow cytometric analysis; 
• 
CT;  
• 
Overall Disease Response; 
• 
Immunogenicity (for subjects receiving KW-0761).  
After progression of disease, subjects will be followed as applicable according to the 
procedures for post-treatment follow-up described in Section 7.5 including collection of 
transplant information for subjects who have received KW-0761. 

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7.7 
Study Procedures for Subjects Continuing Study Treatment at the Time 
of Primary Efficacy Analysis 
Subjects receiving study treatment at the time of the primary efficacy analysis may continue 
on study. For these subjects, administration of study drug(s) and data collection should 
continue as described below.  Note: Initiation of  disease evaluation assessments per 
institution/Investigator standard of care should not occur until notification by the Sponsor. 
Study Drug Administration 
• 
KW-0761 administration: KW-0761 may continue to be administered according to the 
protocol (as specified in Section 8.1) on Day 1 and Day 15 of each cycle until PD, drug 
intolerance or unacceptable toxicity, or until any of the other criteria for study removal 
are met (as defined in Section 5.5) or until KW-0761 is approved/not approved for 
marketing for the indication and regimen under study in the geographic region of study.  
• 
Vorinostat treatment will continue to be administered as described in Section 5.2.2. 
Vorinostat will be supplied by the Sponsor for a period of up to 1 year after the data 
cutoff for the primary efficacy analysis. During this year all study subjects are eligible to 
cross over to mogamulizumab as described in Sections 3.4 and 5.3.  
Safety: Safety data will continue to be collected as described in the protocol for as long as the 
subject receives study drug through 90 days after the last dose or initiation of alternative 
therapy whichever comes first (as described in Section 7.1). 
If a subject who has received KW-0761 undergoes a stem cell transplant at any time during or 
after the 90-day follow-up period, transplant information should be documented as described 
in Section 7.5 including recording of concomitant medications and AEs/SAEs from the 
transplant procedure through 180 days post-transplant. 
Efficacy: Efficacy data will be collected for 1 year after the time of the primary efficacy 
analysis. During that 1-year period, pending notification by the Sponsor, Investigators should 
follow study subjects in accordance with the standard of care at their Institution in order to 
assess subjects’ disease status. Required data collection will be limited to the following 
(additional data may be collected at the discretion of the Investigator): 
• 
At the time of disease progression or discontinuation from treatment for any other reason, 
sites are to perform the disease evaluation assessments per institution/Investigator 
standard of care. The method of assessment of PD, if applicable, should be recorded; 
• 
PRO - Itchy QoL, Skindex-29, EQ-SD-3L, Likert, and FACT-G will be collected every 
4 mos. (16 weeks) for as long as the subject receives study drug. 
In addition, all subjects or their referring physician will continue to be contacted every 
3 months (± 14 days) to ascertain survival status. 

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7.8 
Study Procedures for Subjects Ongoing at the Time of Initial Marketing 
Authorization 
For subjects who are continuing to receive KW-0761 at the time of initial marketing 
authorization, the Sponsor will supply study drug until KW-0761 becomes commercially 
available (reimbursable) in the country/region of the study site or until KW-0761 is not 
approved for marketing for the indication and regimen under study in the country/region of 
the study site.  
Procedures to be followed for all ongoing subjects, i.e., subjects who are continuing to 
receive KW-0761 or who are in safety or survival follow-up, at the time of initial marketing 
authorization are described below.  These procedures should be implemented upon 
notification by the Sponsor.  
Study Drug Administration 
KW-0761 may continue to be administered according to the protocol (as specified in 
Section 8.1) on Day 1 and Day 15 of each cycle until PD, drug intolerance or unacceptable 
toxicity, or until any of the other criteria for study removal are met (as defined in Section 5.5) 
or until KW-0761 becomes commercially available (reimbursable) or is not approved for 
marketing for the indication and regimen under study in the country/region of the study site. 
For subjects who experience an overall CR, the subject may continue treatment for up to 
12 months (as described in Section 5.2.1.4) or until KW-0761 becomes reimbursable or is not 
approved. 
KW-0761 should continue to be administered as described in Section 8.1.3. 
Study Drug Accountability 
Drug accountability must be maintained as described in Section 8.1.6.   
Efficacy and Safety Assessments 
Investigators should follow study subjects in accordance with the standard of care at their 
Institution with respect to assessments of disease status and safety/tolerability, including the 
use of local clinical laboratories.  There will be no further central laboratory requirements. 
Subjects who meet the protocol criteria for progression or relapse in one compartment but are 
clearly deriving benefit in other compartment(s), may remain on treatment at the discretion of 
the Investigator. 
Survival follow-up will be discontinued for all subjects.  

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Data Collection 
Electronic data capture will be terminated for all subjects at the time of implementation of 
Amendment 10.   
Required data collection will be limited to SAEs and treatment-related AEs.  These events 
will be reported only to the KKD Drug Safety Surveillance Department using the SAE form 
(see Section 9.4).   
8 
STUDY AGENTS 
8.1 
KW-0761 (mogamulizumab) 
8.1.1 
Description 
 
 
 
 
  
8.1.2 
Preparation of Dose 
 
 
 
  
 
 
  
 
 
 
 
 
8.1.3 
Study Drug Administration 
Subjects will receive KW-0761 as an iv infusion over at least 1 hour for all infusions. 
Subjects will be observed closely for 1 hour following each administration of KW-0761 for 

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any potential AEs in an area with resuscitation equipment. Vital signs will be checked and 
recorded prior to start of infusion, at the end of the infusion and at 1 hour after completion of 
infusion.  
Hematology results should be reviewed before each subsequent dose. Laboratory assessments 
may be performed the day prior to dosing to ensure results are available prior to dosing. The 
platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 before a subject 
can receive study drug. If a scheduled dose cannot be given within the allowed window, the 
dose should be skipped and the subject should resume dosing with the next scheduled dose 
assuming the platelet count and ANC are within the parameters described above. If a subject 
misses 2 consecutive doses, contact the Medical Monitor or designee to determine if the 
subject should be withdrawn from the trial. 
Should a hypersensitivity reaction to KW-0761 occur, the subject must be treated according 
to the best available medical practices. Subjects should be instructed to report any delayed 
reactions to the investigator immediately. See Section 5.2.1.7 for additional information 
regarding the treatment of infusion reactions. 
8.1.4 
KW-0761 Formulation and Storage 
 
 
 
  
 
  
 
  
8.1.5 
Packaging and Labeling of KW-0761 
 will distribute the study drug to the 
pharmacies at the study sites in the US. 
 
 will distribute the study drug to the pharmacies at the 
study sites in Europe and Australia. 
 will distribute the study drug to 
the pharmacies at the study sites in Japan.  

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8.1.5.1 
Labeling 
Vial and carton labels will bear the appropriate text as required by each country’s regulatory 
agency requirements.  
8.1.6 
Drug Accountability 
The Principal Investigator and pharmacy at the study site are responsible for maintaining 
accurate records of the receipt, dispensing, and return of all investigational materials. The 
Investigator may dispense study drug only to subjects enrolled in the study. Under no 
circumstance will the Investigator allow study drug to be used other than as directed by the 
protocol. 
The pharmacy designated by the Investigator, must maintain an inventory of drug supplies 
received, dispensed, and destroyed. All used and unused study drug must be accounted for. 
When a shipment is received, the Investigator or pharmacist must verify the quantities 
received and return the acknowledgement to the study monitor or designee. The study drug 
accountability record includes the identification of the person to whom the drug is dispensed, 
the lot number on the vial, the date of dispensing, and any returned or unused drug. An 
account must be given of any discrepancies. This record is in addition to information 
regarding dose recorded on the eCRF. These records must be readily available for inspection 
by KKD monitor or designee and are open to FDA or other regulatory authority inspection at 
any time. Copies of this record will be provided to the sponsor by the Investigator at the 
conclusion of the study. 
8.1.7 
Return and Destruction 
Upon completion or termination of the study, all unopened vials of KW-0761 must be 
destroyed at the study site according to local regulations, unless other arrangements have 
been approved by KKD. 
8.2 
Vorinostat (ZOLINZA®) Capsules 
8.2.1 
Description 
Vorinostat will be supplied by the Sponsor for a period of up to 1 year after 255 PFS events 
are observed. Vorinostat is a white to light orange powder. Each 100 mg capsule for oral 
administration contains 100 mg vorinostat and the following inactive ingredients: 
microcrystalline cellulose, sodium croscarmellose and magnesium stearate. The capsule shell 
excipients are titanium dioxide, gelatin and sodium lauryl sulfate. This agent is approved for 

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marketing in the US, Japan and Australia and is indicated for the treatment of progressive, 
persistent or recurrent CTCL. Since vorinostat is not approved in the EU, it will be labeled as 
an investigational drug according to applicable regulations. Investigators will use the supplies 
provided and will follow the FDA approved US prescribing information (e.g., dosage and 
administration, warnings, precautions, adverse reactions, dose modifications and omissions 
and storage information).  
8.2.2 
Administration 
Subjects will receive 400 mg daily of vorinostat orally with food commencing on Day 1. 
8.2.3 
Vorinostat Adverse Events  
The most common AEs (≥ 20%) are diarrhea, fatigue, nausea, thrombocytopenia, anorexia 
and dysgeusia. Please refer to the US prescribing information for more complete information. 
8.2.4 
Return and Destruction 
Upon completion or termination of the study, all unopened containers of vorinostat must be 
destroyed at the study site according to local regulations, unless other arrangements have 
been approved by KKD. 
9 
ADVERSE EVENT REPORTING IN CLINICAL TRIALS 
The Investigator will inquire about AEs at all subject visits by asking the subject a question 
such as: “How have you been feeling since your last visit?” All AEs, whether observed by the 
Investigator or reported by the subject, must be collected and recorded on the appropriate AE 
page of the eCRF and as appropriate on the SAE form (see Section 9.2). (See Section 7.8 for 
reporting requirements/procedures for subjects who are ongoing in the study (i.e., subjects 
who are continuing to receive KW-0761 or who are in safety or survival follow-up) at the 
time of initial marketing authorization). 
The collection of AE information commences following the subject’s written Informed 
Consent to participate in the study. If a subject experiences an AE, the subject will receive 
appropriate treatment and supportive care as necessary, and the Investigator will continue to 
follow up until there is a return to the subject’s baseline condition, or until a clinically 
satisfactory resolution is achieved. 
Timely and complete reporting of all AEs assists the Sponsor in identifying any untoward 
medical occurrence, thereby allowing: (1) protection of safety of study subjects; (2) a greater 

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understanding of the overall safety profile of the study drug; (3) recognition of dose-related 
study drug toxicity; (4) appropriate modification of study protocols; (5) improvements in 
study design or procedures; and (6) adherence to worldwide regulatory requirements. Every 
effort should be made to enter the AE information in the eCRF within 7 days of when the 
information becomes available in order to ensure timely reporting to the Sponsor. 
9.1 
Definitions 
9.1.1 
Adverse Events 
An AE is any untoward medical occurrence in a clinical investigation subject administered an 
investigational product and which does not necessarily have to have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding, for example), symptom or disease temporally associated with 
the use of an investigational product, whether or not considered related to the investigational 
product. 
The description of each AE will identify the subject, date of onset, the date of resolution, the 
severity of the event, the action taken regarding study drug, the outcome of the event, and the 
relationship of the event to study drug. A medical condition present at screening that has 
increased in frequency or severity must be recorded on the AE page of the eCRF. 
Standard medical terminology should be used to document AEs on the eCRF. The subject’s 
exact description of the event will be recorded in the source documentation. In the case of 
signs and symptoms, the underlying illness or diagnosis will be recorded as the event when 
known. 
For this study, disease progression will not be considered as an AE. Lymphopenia is the 
pharmacologic effect of the drug and will also not be considered an AE for this study. 
Lymphocytes will be monitored and evaluated with the laboratory data. 

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9.1.2 
Adverse Event Severity 
All AEs will be graded using CTCAE Version 4.0 as:  
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADLa 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADLb 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE 
a: Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
b: Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
ADL=Activities of Daily Living 
 
For AEs not contained within CTCAE, Version 4.0, the Investigator will assess the 
severity/grade of an AE according to the five grades above. 
9.1.3 
Adverse Event Relationship to Study Drug 
The relationship of each AE to the study drug will be evaluated using the following 
guidelines: 
Definitely Related 
An AE that follows a reasonable temporal sequence from administration of the drug 
(including the course after withdrawal of the drug) and that satisfies any of the following: 
(1) reappearance of a similar reaction upon re-administration (positive re-challenge); 
(2) positive results in a drug sensitivity test (skin test, etc.); (3) toxic level of the drug as 
evidenced by measurement of drug concentrations in blood or other bodily fluid. 
Probably Related 
An AE that follows a reasonable temporal sequence from administration of the drug 
(including the course after withdrawal of the drug) and for which involvement of factors 
other than the drug, such as underlying diseases, complications, concomitant drugs and 
concurrent treatments, can reasonably be excluded. This may also include positive 
dechallenge (event abates upon discontinuation of the investigational agent). 

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Possibly Related 
An AE that follows a reasonable temporal sequence from administration of the drug 
(including the course after withdrawal of the drug) and for which possible involvement of the 
drug can be suggested (for example previous similar reports or pharmacologic actions of the 
drug) although factors other than the drug, such as underlying diseases, complications, 
concomitant drugs and concurrent treatments may also be responsible.  
Unlikely 
An AE that, while relationship to the drug cannot be definitively excluded, does not appear to 
follow a reasonable temporal sequence from administration of the drug or that appears to be 
reasonably explained by other factors, such as underlying diseases, complications, 
concomitant drugs and concurrent treatments. 
Not Related 
An AE that does not follow a reasonable temporal sequence from administration of the drug 
or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs and concurrent treatments. 
As of Amendment 10, relationship to study drug will be reported as related/not related per 
SAE form requirements (see Section 7.8). 
9.2 
Serious Adverse Events 
Any AE that is initially considered serious or becomes serious should be reported on the SAE 
form.  
A SAE is any untoward medical occurrence which: 
• 
Results in death; 
• 
Is immediately life threatening;  
– The term “life-threatening” in the definition of “serious” refers to an event in which 
the subject was at risk of death at the time of the event; it does not refer to an event 
that hypothetically might have caused death if it were more severe.  
– If an event is Grade 4 by CTCAE version 4.0, it does not necessarily meet the 
definition for life-threatening. 
• 
Requires in-patient hospitalization/admission or prolongation of existing hospitalization; 
• 
Results in persistent or significant disability/incapacity;  
• 
Is a congenital anomaly/birth defect; or 
• 
Is an important medical event: 

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– Those events that may not be immediately life-threatening or result in death or 
hospitalization but based upon appropriate medical and scientific judgment may 
jeopardize the subject or may require intervention to prevent one of the serious 
outcomes listed above. Examples include intensive treatment in an emergency room 
or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization; development of drug dependency or drug abuse. 
All AEs, whether non-serious or serious, must be recorded on the AE page of the eCRF. In 
addition, any AE that is initially considered serious or becomes serious must be reported on 
the SAE form. The SAE information entered on the eCRF must be consistent with the 
information entered on the SAE form. 
Serious adverse events require expeditious handling to comply with regulatory requirements. 
Any SAE occurring in a clinical study subject must be reported to the Sponsor or designee 
within 24 hours of the Investigator having knowledge of the SAE. 
The Investigator or other qualified individual at the investigative site must complete the SAE 
form and fax it to the Sponsor or designee. All telephone communication regarding an SAE 
must be followed by a written report. In addition, SAE reports may require subsequent 
notification of the IRB and/or Ethics Committee (EC), if appropriate. 
The Investigator is obligated to immediately report to the Sponsor or designee any SAE 
occurring at any time after the subject signs the Informed Consent Form and within 90 days 
after the last dose of study drug or initiation of alternative therapy whichever comes first, 
independent of the circumstances or suspected cause. In all subjects who cross over from 
vorinostat to KW-0761, the causality should be assessed for both drugs for 30 days after 
vorinostat was stopped (or later if the event is considered to be related to vorinostat). In 
addition, the Investigator must promptly report to the Sponsor any SAE occurring at any 
other time after completion of the study if a causal relationship to study drug is suspected. 
For all SAEs, the Investigator is obligated to pursue and provide information as requested by 
the Sponsor in addition to that requested on the SAE form. Information must include a 
description of the SAE in sufficient detail to allow for a complete medical assessment of the 
case and independent determination of causality. In the case of a subject death, a summary of 
autopsy findings, if available, must be submitted as soon as possible to the Sponsor. The 
Investigator will ensure that information reported immediately by telephone or other means 
and information entered on the SAE form is accurate and consistent.  

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9.3 
Other Safety Considerations 
Any clinically important changes noted during interim or final physical examinations, ECGs, 
x-rays, or any other potential safety assessments, whether or not these procedures are 
required by the protocol, must also be recorded on the appropriate eCRF page and SAE form, 
as appropriate, in order for the Sponsor to collect additional information about that 
abnormality, including information regarding relationship to study drug, any action taken, 
and resolution.  
9.4 
Adverse Event Contacts 
All non-emergency inquiries and general information regarding this study should be directed 
to the Sponsor or designee.  
Serious adverse event reports and follow-up SAE documentation for subjects in the US, UK, 
and Australia should be forwarded to the KKD Drug Safety Surveillance Department:  
 
 
 
 
Serious adverse event reports and follow-up SAE documentation for subjects in Japan should 
be forwarded to the KHK Drug Safety Surveillance Department: 
 
9.5 
Data Safety Monitoring Board 
A Data Safety Monitoring Board (DSMB), whose composition, roles and responsibilities are 
described in a separate DSMB charter, will oversee subject safety in the trial. The DSMB 
consists of at least 2 medical doctors and a statistician.  
10 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
The number of subjects enrolled and discontinued will be presented. A summary of reasons 
for discontinuation will be provided. The number of subjects in the Intent-to-Treat (ITT), 
Safety Analysis, and Efficacy Evaluable Sets (see Section 10.1) will be presented by 
treatment arm and combined.  

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Demographic and other baseline subject characteristics will be summarized by treatment arm 
for the ITT Set. These summaries will include demographics (including age, race, sex, height, 
weight, and body surface area) and baseline values for disease information. 
Descriptive statistics (mean, standard deviation, median, minimum, and maximum) for 
continuous variables and frequency distributions and percentages for discrete variables will 
be utilized. 
10.1 Populations to be Analyzed 
The following analysis sets will be used in the study: 
• 
Intent-to-Treat Set: Includes all subjects randomized to a therapy and assigned a study 
number. 
• 
Safety Analysis Set: Includes all subjects who received at least one dose of the assigned 
study agent (even a partial dose).  
• 
Efficacy Evaluable Set: Includes all subjects who receive the first cycle of treatment and 
who have baseline and the Day 26-28 on-study assessment for response.  
• 
Pharmacokinetic (PK) Analysis Set:  All subjects who provide at least one post-dose 
KW-0761 concentration measurement will be included in the PK analysis dataset.  
10.2 Analyses of Safety Data 
The safety and tolerability of KW-0761 and vorinostat is determined by reported AEs, 
physical examinations, ECGS, vital signs, and laboratory tests. All summaries for the Safety 
Analysis Set will be prepared for each treatment arm. For those subjects in the vorinostat arm 
who cross over to KW-0761 treatment arm, AEs with an onset date/time after the first dose of 
KW-0761 will be summarized separately within that KW-0761 crossover group. 
The World Health Organization (WHO) Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class and Preferred Term. Prior medications include 
medications that were taken within 30 days prior to the Pre-treatment Visit. Concomitant 
medications include medications that started at any time and were taken at any time after the 
start of treatment until the end of the entire treatment period. 
Adverse events are collected from the time the subject signs the ICF until 90 days after the 
last dose or initiation of alternative therapy, whichever comes first. In all subjects who cross 
over from vorinostat to KW-0761, the causality should be assessed for both drugs for 30 days 
after vorinostat was stopped (or later if the event is considered to be related to vorinostat). 
The NCI-CTCAE v4.0 system will be used to grade AEs. Treatment-emergent AEs will be 
grouped and tabulated by MedDRA preferred terms and system organ class. AEs will be 

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classified by body system, incidence, severity, and causality. All treatment-emergent AEs 
will be summarized showing the number and percent of subjects for each outcome. 
The results from physical examination will be presented in the subject data listings. Vital sign 
measurements will be summarized at each time point. The incidence of clinically significant 
laboratory abnormalities will be presented, and laboratory data will be summarized at each 
time point by the NCI-CTCAE v4.0 toxicity grade. Laboratory data will be presented for 
subjects having Grade 3 or 4 changes from baseline by treatment arm.  
Pre- and post-treatment serum samples will be assayed for development of human antibodies 
to KW-0761 (anti-KW-0761). 
10.3 Analyses of Efficacy Data 
Disease status will be assessed every 4 weeks in skin and blood. In the first year of treatment, 
response in lymph nodes and viscera and the overall global composite score will be 
documented every 8 weeks. After the first year, response in the lymph nodes and viscera and 
the overall global composite score will be documented every 16 weeks. Additionally, if 
clinical progression is noted, efficacy assessments are performed to fully document disease 
progression.  
These assessments will be compared with the baseline assessment to determine response. 
Subjects will be evaluated for response in each compartment. Progressive-free survival, 
overall response, duration of response, and QoL will be analyzed. For any time-to-event 
endpoints, the date of disease progression will be determined by both the on-site 
investigator’s assessment and the IR. All efficacy analyses will be conducted on both the ITT 
and Efficacy Evaluable sets.  
The primary comparison of PFS between both arms will be performed on the ITT set based 
upon the results of the on-site investigator’s assessment using a stratified Log-rank test at the 
one-sided 2.5% significance level. Stratification is done by disease type, either SS or MF, and 
disease stage, either IB/II or III/ IV. A similar secondary analysis will be performed on the 
results based on the IR. Each analysis will also be conducted for the Efficacy Evaluable Set. 
Progressive-free survival, which will be analyzed using Kaplan-Meier survival analysis 
methods, is defined as the time from the day of randomization to a treatment arm until 
documented progression or death. For subjects who exhibit conditions of disease progression, 
but continue on the study due to a questionable clinical impression as described in Sections 
5.2.1.4 and 5.2.2.3, the subject is not considered to have progressed unless disease 

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progression is confirmed at least 4 weeks after the date of the initial questionable disease 
progression. In this case, the initial date will be used as the date of disease progression.  
For PFS events, all deaths will be attributed to progression and, hence, the TTP will equal the 
time to death and will be uncensored. Subjects who die without a reported prior progression 
will still be considered to have progressed on the day of their death. In the event that a 
randomized subject withdraws from the study for any reason before documented progression, 
the time from the day of randomization to the last tumor assessment (from any compartment) 
will be used as a censored time point. For all subjects randomized to a treatment arm but 
withdrawing prior to first tumor assessment for any reason other than disease progression, the 
PFS time will be censored at the last documented visit. Sensitivity analyses for PFS will be 
performed, with the details specified in the Statistical Analysis Plan. 
Frequency tables will be used to display best response. Best response will be presented for all 
subjects by treatment arm. The best overall response is the best response from the start of 
treatment until disease progression/recurrence. The subject’s best response assignment will 
depend on the achievement of both measurement and confirmation criteria. Response data 
will be analyzed for both the ITT and the Efficacy Evaluable Set for each treatment arm. 
Exact 95% confidence intervals for response rate will be calculated for each of these groups 
along with the difference in response rates between the 2 treatment arms. All 95% confidence 
intervals on individual rates will be computed using exact computational methods. Any 
confidence interval on the difference of proportions will be computed using exact 
unconditional confidence limits for the risk difference. These confidence intervals can be 
constructed using SAS version 9.2 with the FREQ procedure specifying the RISKDIFF 
option in the EXACT statement (Santner, 1980). ORR will be calculated as the proportion of 
subjects who are responders (CR and PR) and the 95% exact confidence interval for response 
will be calculated. 
The duration of response (DOR), which will be estimated using survival analysis methods, is 
measured from the time measurement criteria are met for CR/PR (whichever is first recorded) 
until the first date that PD or death is objectively documented (taking as a reference for PD 
that smallest measurement recorded since the treatment started). Subjects who do not relapse 
will be censored at the day of their last tumor assessment. The DOR will be estimated 
separately for each treatment arm. Because the DOR is a conditional estimate (conditional on 
having a response), comparison between KW-0761 and vorinostat would not be based on 
randomized groups and therefore will not be made. 

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The Pruritus Evaluation (Likert scale & Itchy QoL) and Skindex-29, FACT-G and EQ-5D-3L 
assessments will be summarized at baseline and at the timepoints specified in the study 
procedures tables for each arm. The improvement (change from baseline) for each of these 
measures will also be summarized and analyzed using repeated measures ANCOVA utilizing 
time points through the 6-month assessment.  
For those subjects who crossover from the vorinostat arm to the KW-0761 arm, these 
assessments within the second arm of the study will be measured at the end of the first cycle 
after the first day of dosing for KW-0761. Baseline measurements for crossover subjects are 
those documented closest to and before the first KW-0761 infusion. No statistical 
comparisons will be made for information gathered in the crossover from the vorinostat arm 
to the KW-0761 arm. All summaries for this arm will be purely descriptive. 
Progression-free survival is the primary endpoint in this study. There are four key secondary 
endpoints in this study that require a comparison between treatment arms: ORR, Skindex-29, 
FACT-G, and EQ-5D-3L. Comparisons of these four secondary endpoints between the 
2 treatment arms will be conducted using p-values that are adjusted to control the overall 
study-wise Type 1 error rate to be less than 0.05. Since these tests are not independent, the 
four secondary tests will be conducted using the Sidak adjusted p-value method defined as  
Adjusted p-value = 1-(1-p)4 where p is the original p-value of the individual test 
These adjusted p-values will then be compared to .05 for each test. 
Comparisons between treatment arms for all other secondary endpoints such as Likert scale, 
and Itchy QoL will be conducted with no adjustment for multiple comparisons used for those 
statistical tests. Exploratory subset analyses for PFS and any of the secondary endpoints by 
region, study site, compartment involvement, CCR4 expression status, disease subtypes, and 
medical history may be conducted. Details of such subset analyses will be provided in the 
Statistical Analysis Plan. Although overall survival (OS) is not a secondary endpoint, each 
subject will be followed in this study for a minimum of 2 years to generate information on 
OS. Using this follow-up information, a comparison between treatment arms for OS will also 
be conducted and considered exploratory. Statistical analyses on OS using follow-up data 
may take place after database lock for the study and will be reported as supplemental to the 
Clinical Study Report. 
Randomization will be stratified within the 2 disease types, SS and MF and 2 disease stages 
IB or II and III or IV. The efficacy analyses described in this section will be conducted as 
stratified tests but may also be conducted as a subset analysis within each of these 
disease-type groups and disease stages. Comparison of endpoints between these 2 groups and 

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stages will be conducted for each treatment assuming adequate sample sizes in the respective 
groups. 
Exploratory analyses based on other subject groupings and with other parameters may also be 
conducted. 
Since the primary endpoint is PFS, the reference median PFS for vorinostat is assumed to be 
169 days. The median PFS for KW-0761 therapy is targeted for 254 days, a 50% 
improvement over this reference median. For a 24-month accrual and 12 month follow-up on 
the last subject dosed, Table 10.3-1 gives the power and the number of PFS events required to 
show superior PFS for KW-0761 therapy over vorinostat at the one-sided 0.025 significance 
level. The ITT set is used for this primary analysis. The same analysis conducted using the 
Efficacy Evaluable set is considered secondary. 
Under these assumptions, for the ITT population, a total of 255 PFS events will give 90% 
power (row is in bold in Table 10.3-1). For this study, the final primary analysis comparing 
PFS between treatment groups will not be conducted until 255 PFS events occur or until a 
maximum of 24 months after the last randomized subject’s first dose, whichever comes first. 
In the event that the study is stopped prior to 255 PFS events are observed, the primary test 
will be performed at less than 90% power under the current assumptions according to 
Table 10.3-1. 
Each of these calculations uses a log-rank test to compare the 2 survival curves. Sample size 
calculations were computed using SAS software version 9.3 using PROC POWER, 
Twosamplesurvival test = logrank. 

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Table 10.3-1 Required PFS Events and Power for Comparison of PFS Kaplan-Maier 
Curves Between the Vorinostat and KW-0761 Arms at the 0.025 Level 
Vorinostat Median PFS = 169 Days, KW-0761 Median PFS = 254 Days 
Power 
Total Required PFS 
Events  
Expected Total Sample Size to Achieve The Required 
Events 
90 
255 
288 
89 
247 
280 
88 
239 
270 
87 
231 
262 
86 
225 
254 
85 
218 
248 
84 
212 
240 
83 
206 
234 
82 
201 
228 
81 
196 
222 
80 
191 
216 
The total sample size of 288 represents the approximate number of subjects that may be 
necessary for 255 PFS events to occur within the projected 36 months of the trial. If a 10% 
inflation factor is applied to this total (about 29 subjects) to take into account those subjects 
that may be lost to follow-up prior to documented progression, a total of 317 enrolled 
subjects may be necessary in order to observe 255 PFS events.  
The observed rates of PFS events, recruitment, and drop-outs will be monitored throughout 
the study and may be used to alter the number of sites, the accrual period, and the follow-up 
period to achieve the required 255 PFS events in a timely manner. If the 255 PFS events are 
not observed within 36 months from the start of enrollment the study will be stopped at 
approximately 24 months after the last randomized subject’s first dose.  
10.4 Exposure-Response Analysis 
Values for individual drug concentrations and descriptive statistics for each blood sample for 
PK assessment will be provided at each scheduled time point of collection. 
Exposure-response analysis using population-based methods will be presented in a separate 
report. 
11 
ETHICAL ASPECTS 
11.1 Ethics and Good Clinical Practice 
This study will be conducted in compliance with the International Conference on 
Harmonization (ICH) E6 Good Clinical Practice (GCP) guidance, and the most recent version 

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of the Declaration of Helsinki as amended in 2008. In addition, all applicable local laws and 
regulatory requirements relevant to the use of new therapeutic agents in the countries 
involved will be adhered to. 
11.2 Ethics Committee/Institutional Review Board 
Prior to implementation of the study, the protocol and the proposed informed consent form 
must be reviewed and approved by a properly constituted EC/IRB. A dated statement that the 
protocol and informed consent have been approved by the EC/IRB must be provided to the 
Sponsor prior to study initiation. Any amendments to the protocol will also require EC/IRB 
approval, except in the case of changes made to protect subject safety, which may be 
implemented immediately. The name and occupation of the chairperson and the members of 
the EC/IRB will be provided. 
The Investigator will provide progress reports to the EC/IRB as required by the EC/IRB. The 
Investigator will provide a final report to the EC/IRB within three months after completion of 
participation in the study.  
The Investigator will not start this study, nor will study drug be shipped to the Investigator’s 
site, before providing the Sponsor or designee with evidence of EC/IRB approval. 
11.3 Informed Consent 
The Investigator must explain to each subject the research nature of the study, its purpose, 
procedures, expected duration and the potential risks and benefits involved in study 
participation. Each subject must be informed that participation in the study is voluntary and 
that he/she may withdraw from the study at any time and that withdrawal of consent will not 
affect his/her right to the most appropriate medical treatment or affect the doctor/subject 
relationship. 
The informed consent should be given by means of a standard written statement. The 
informed consent document should be written so as to be easily understood by the subject or 
the subject’s legal representative. The subject or the subject’s legal representative should be 
given time to read and understand the information before signing the informed consent 
document. The subject should receive a copy of the written informed consent document once 
he/she has signed. 
If signed consent is not possible, then it is also possible to obtain consent orally, in which 
case, the act of informed consent should be established by an additional signed statement 
from an independent witness. The Investigator should explain in the chart why direct-signed 

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consent was not possible. Each investigator must provide a copy of the signed informed 
consent form to the subject. A subject may not be admitted to the study unless informed 
consent of the subject (or his/her legally authorized representative) has been obtained. 
Subjects will be asked to consent to allow the sponsor, sponsor representative or regulatory 
auditor to review their medical records to confirm compliance with GCP and the protocol. 
The standard written informed consent statement forms a part of the protocol that is 
submitted to the EC/IRB for approval. The Investigator must submit a specimen copy of the 
EC/IRB-approved informed consent document to be used in the study before the study is 
initiated.  

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12 
INVESTIGATOR OBLIGATIONS AND STUDY MANAGEMENT 
12.1 Administrative 
All references to KKD in this section include all designees e.g., Contract Research 
Organizations or Consultants acting on behalf of KKD. 
12.2 Changes in Protocol 
Any change to the protocol will be made by written amendment to the Investigational New 
Drug Application (IND) and Clinical Trial Authorization (CTA) (if required) and approved 
by KKD and the Principal Investigator(s) before the change is implemented. All amendments 
to the protocol and informed consent form, which require regulatory and/or EC/IRB 
approval/favorable opinion, must be reviewed and approved by KKD, the EC/IRB and/or 
local authorities before being implemented. Amendments should not be implemented until all 
necessary approvals have been obtained, except when necessary to eliminate an immediate 
hazard(s) to study subjects.  
12.3 Protocol Deviations  
KKD, as the protocol sponsor, is responsible for implementing and maintaining quality 
assurance and quality control to ensure that studies are conducted according to the protocol, 
GCPs and all applicable regulatory requirements. A protocol deviation is any noncompliance 
with the protocol. Noncompliance can be on the part of the study participant, the Investigator 
or the study site staff. Deviations to the protocol are not permitted except when necessary to 
eliminate an immediate hazard(s) to study subjects.  
12.4 Monitoring and Quality Assurance 
The Sponsor of this study, KKD, has responsibilities to health authorities to take all 
reasonable steps to ensure the proper conduct of the study as regards to ethics, protocol 
adherence, integrity, validity of the data recorded on the eCRF and adherence to regulations 
regarding GCP and the protection of human subjects.  
If the study site has not participated in a KKD sponsored trial within the past year, KKD or 
its designee will assess the study site prior to study initiation to verify the qualifications of the 
Investigator, inspect the study site’s facilities and inform the Investigator of his/her 
responsibilities and the procedures for ensuring adequate and correct documentation.  

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During the course of the study, the study monitor will make routine site visits to review 
protocol compliance, compare eCRFs with individual subject’s original source documents, 
assess drug accountability and ensure that the study is being conducted according to the 
pertinent regulatory requirements. The review of the subject’s medical record will be 
performed in a manner to ensure that the subject’s confidentiality is maintained. Monitoring 
visits will occur approximately every 6-8 weeks. Frequency of visits may be modified based 
on the rate of enrollment or as otherwise necessary to ensure GCP compliance. The 
Investigator agrees to cooperate with the monitor to ensure that any problems detected in the 
course of these monitoring visits, including delays in completing case report forms, are 
resolved. 
Regulatory authorities and/or the KKD staff may carry out source document verification 
visits and/or site inspections/audits. Direct access to original source data will be required for 
inspections/audits, which will be carried out giving due consideration to data protection and 
subject confidentiality. 
12.5 Electronic Case Report Forms (eCRFs) and Source Documentation 
The investigator is required to prepare and maintain adequate and accurate case histories (i.e., 
medical records) designed to record all observations and other data pertinent to the study for 
each study participant.  
It is the responsibility of the Principal Investigator to prepare and maintain adequate and 
accurate eCRFs that have been designed by the Sponsor to record all observations and other 
data pertinent to the clinical investigation.  
Electronic Case Report Forms are used to record information collected in the performance of 
this study and to transfer the data into the study database. These eCRFs are organized as an 
ordered series of electronic data entry modules specific for each scheduled and unscheduled 
study visit.  
The electronic data capture (EDC) users at the study site will exercise due diligence in 
ensuring that study subject data are entered accurately and in their entirety from the 
investigative site’s source documents and flow sheets into the appropriate data entry fields. 
Only staff listed on the “Delegation of Authority” page in the study file notebook and who 
have been appropriately trained will be issued a user ID enabling them to make entries and 
edits to the electronic trial database and to respond to queries. Only the Principal Investigator 
will be issued a user ID allowing the application of an electronic signature to a completed 

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study subject record signifying the data has been reviewed and verified as complete and 
accurate. 
Upon completion of the study, validated study subject records will be published 
electronically along with the Principal Investigator’s electronic signature in a Portable 
Document Format (PDF) file and transferred to a CD-ROM. The compact disc(s) will then be 
distributed to the Study Site to be retained by the Principal Investigator as a component of the 
required records for this study. 
At the time of implementation of Amendment 10, the electronic data capture system defined 
as the clinical database will be terminated for all subjects (see Section 7.8). 
12.6 Record Retention 
Study data and other essential documents should be retained by the study site for a minimum 
of 2 years after the last approval of a marketing application in an ICH region and until there 
are no pending or contemplated marketing applications in an ICH region or until at least 
2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product. However, these documents should be retained for a longer period if 
required by the applicable legal requirements. KKD or its designee will inform the 
investigator, in writing, as to when these documents no longer need to be maintained. 
12.7 Confidentiality  
All personal data collected and processed for the purposes of this study should be managed 
by the investigator and his/her staff with adequate precautions to ensure the confidentiality of 
those data, and in accordance with applicable national and/or local laws and regulations on 
personal data protection. 
Monitors, auditors, and other authorized agents of KKD and/or its designee, the EC/IRBs 
approving this research, and the regulatory authorities, as well as that of any other applicable 
government agency(ies), will be granted direct access to the study subjects’ original medical 
records for verification of clinical trial procedures and/or data, without violating the 
confidentiality of the subjects, to the extent permitted by the law and regulations. In any 
presentations of the results of this study or in publications, the subjects’ identity will remain 
confidential. 

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12.8 Disclosure 
By conducting this study, the Investigator agrees that all information provided will be 
maintained by the Investigator and his/her staff in strict confidence. Such information may be 
communicated to the Scientific Committee and/or EC/IRB under a similar, appropriate 
understanding of the confidential nature of the information. Study documents provided 
(protocols, IBs, case report forms and other material) will be stored appropriately to ensure 
their confidentiality. It is understood that the confidential information provided to the 
Investigator will not be disclosed to others without written authorization from KKD, except 
to the extent necessary to obtain informed consent from those subjects who are eligible and 
choose to participate in the study.  
Such information will not be provided to potential subjects by telephone or to any other 
individual. 
12.9 Termination of Study 
The Sponsor reserves the right to terminate the study or individual study sites at any time. 
Reasons for study termination include, but may not be limited to, manufacturing problems, a 
request to discontinue the study from a regulatory authority, a corporate decision to 
discontinue development of KW-0761, AE incidence or severity not consistent with the 
potential benefit of the drug, poor enrollment or inadequate adherence to GCP guidances. In 
terminating the study, the Sponsor and the Principal Investigator will assure that adequate 
consideration is given to the protection of the subjects’ interest. If the trial is terminated 
prematurely, the EC/IRB and regulatory authorities (if required) will be notified.  
12.10 Final Report/Publications 
The study is part of a multicenter study; accordingly, the Institution and Principal Investigator 
of the study agree that the first publication of the results of the study shall be made in 
conjunction with the presentation of a joint, multicenter publication of the study results with 
the Investigators and the Institutions from all appropriate sites contributing data, analyses and 
comments. However, if such a multicenter publication is not submitted within 12 months 
after the database has been locked, abandonment or termination of the study at all sites, or 
after Sponsor confirms there will be no multicenter study publication, the Institution and/or 
such Principal Investigator may publish the results from the institution site individually in 
accordance with the following requirements. Prior to submission of any materials for 
publication or presentation, the Institution will provide such materials or manuscript to the 

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Sponsor for review. Details of the Sponsor’s publication policy can be found in the Clinical 
Trial Agreement. 

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13 
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Yagi H, Naohiro S, Ohshima A, Itoh T, Itoh N, Horibe T, et al. Chemokine receptor 
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APPENDICES 

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Appendix 1 
Modified ISCL/EORTC Revisions to the TNMB Classification of 
MF/SS 
 
 
 

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Appendix 2 
Eastern Cooperative Oncology Group (ECOG) Scale 

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Appendix 3 NYHA Classification 
 

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Appendix 4 
Autoimmune Screening Questionnaire 
 

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Appendix 5 
Itchy Quality of Life Questionnaire  
 

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Appendix 6 
Skindex-29  

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Appendix 7 
FACT-G 

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Appendix 8 
EQ-5D-3L 
 

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Appendix 9 
Likert Scale for Pruritus Evaluation