Clinical trial NCT01961882
Conditions: Acute Myeloid Leukemia
Keywords: OCV-501 Acute Myeloid Leukemia Antigen specific cancer immunotherapeutic
Sponsor: Otsuka Pharmaceutical Co., Ltd.
Start date: 2013-10-01; Completion date: 2017-11-16
Enrollment: 134 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To compare disease-free survival in patients 60 years or older with acute myeloid leukemia (AML) who are randomly assigned to receive either OCV-501 monotherapy or placebo.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: OCV-501 intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
 
 
CLINICAL STUDY PROTOCOL 
 
 
 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Phase 2 Trial to Evaluate the Efficacy and Safety of OCV-501 in 
Elderly Patients With Acute Myeloid Leukemia 
 
 
 
 
NCT Number: NCT01961882 
PRT NO.: 311-12-001 
Version Date: 07 July 2015 (Version 7.0) 


Protocol No. 311-12-001 
 
 
 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Phase 2 Trial to Evaluate the Efficacy and Safety of OCV-501 in 
Elderly Patients With Acute Myeloid Leukemia  
 
 
Clinical Protocol 
Protocol No.: 311-12-001 
 
 
Confidential 
 
 
 
Otsuka Pharmaceutical Co., Ltd. 
2-9 Kanda-Tsukasamachi, Chiyoda-ku, Tokyo 101-8535, Japan 
 
Version 1.0: 29 Jul 2013 
Version 2.0: 19 Aug 2013 
Version 3.0: 7 Feb 2014 
Version 4.0: 28 Feb 2014 
Version 5.0: 24 Jun 2014 
Version 6.0: 27 Oct 2014 
Version 7.0: 7 Jul 2015 


Protocol No. 311-12-001 
 
Statement of Confidentiality 
The trial protocol is to be treated as confidential information and is to be made available 
only to persons involved in the trial.  The content of the protocol is not to be disclosed to 
any third party without the prior written consent of Otsuka Pharmaceutical Co., Ltd., 
except in the case of its being explained to a candidate trial subject.  Disclosure of the 
results of the trial to academic societies or journals, etc, in part or in whole, will require 
the prior written approval of Otsuka Pharmaceutical Co., Ltd. 
 


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Trial Protocol Synopsis 
Name of Test Product 
OCV-501 
Trial Title 
A multicenter, randomized, double-blind, placebo-controlled, 
phase 2 trial to evaluate the efficacy and safety of OCV-501 in 
elderly patients with acute myeloid leukemia. 
Trial Objectives 
Primary:  
To compare disease-free survival in patients 60 years or older 
with acute myeloid leukemia (AML) who are randomly assigned 
to receive either OCV-501 monotherapy or placebo. 
Secondary:  
 To compare overall survival between both treatment arms 
 To compare patient quality of life (European Organization for 
Research and Treatment of Cancer [EORTC] QLQ-C30) and 
performance status (Eastern Cooperative Oncology Group 
performance status [ECOG PS]) between both treatment arms 
 To characterize and compare safety in the both treatment arms 
 To assess immunological responses (OCV-501-specific IFN-γ 
production, WT1-killer peptide specific IFN-γ production, 
anti-OCV-501 antibody level, anti-WT1 antibody level), 
immunoglobulin 
 To assess WT1 mRNA level 
Phase of Development 
Phase: 2 
Type of trial: Exploratory trial 
Trial Design 
A multinational, multicenter, randomized, double-blind, placebo-
controlled trial 
Target Disease 
Acute myeloid leukemia 
Target Number of 
Subjects 
120 patients (60 patients in OCV-501 arm and 60 patients in 
placebo arm)  
Inclusion Criteria 
Patients who meet all of the following criteria at the time of 
enrollment will be selected. 
1) Patients with AML (WHO classification 2008) who achieved 
first complete remission within one or two courses of standard 
induction therapy*, and completed standard consolidation 


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therapy* (one or more courses).  
* Induction therapy and consolidation therapy are according to the institution's 
standard of care. 
 Applicable types of disease for this trial in WHO 
classification  
 AML with recurrent genetic abnormalities 
 AML, myelodysplasia-related changes 
 AML, not otherwise specified 
2) Patients who are 60 years or older at the time of providing 
informed consent 
3) Sex: Male or female 
4) Patients with an Eastern Cooperative Oncology Group 
(ECOG) performance status of 0 - 2 at the time of trial 
enrollment 
5) Patients with no significant impairments in the functions of 
major organs (as indicated by laboratory values) meeting the 
following criteria within 3 weeks of investigational medicinal 
product (IMP) administration: 
 Hematological functions 
Patients must not require administration of a blood-derived 
product or blood transfusion, or granulocyte colony-stimulating 
factor (G-CSF), granulocyte macrophage colony-stimulating 
factor (GM-CSF). 
 Neutrophil count: > 1,000/μL,   
 Platelet count: > 50,000/μL 
 Hepatic functions  
 AST and ALT: < 5 × the upper limit of normal (ULN) 
 Total bilirubin: < 3 × ULN 
 Renal function 
 Serum creatinine: < 3 × ULN 
6) Patients with a life expectancy of at least 3 months 
7) Patients who have provided written informed consent within 
90 days from the last dose of consolidation therapy on an 
informed consent form that has been approved by an 
institutional review board or independent ethics committee 
Exclusion Criteria 
Patients who fall under any of the following exclusion criteria at 
the time of enrollment will be excluded from participation in the 
trial. 


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1) Patients who have acute promyelocytic leukemia (APL) with 
t(15;17)(q22;q12), (PML/RARA) karyotype abnormalities, 
and other variant types. 
2) Patients who are scheduled for hematopoietic stem cell 
transplantation 
3) Patients who have undergone cancer immunotherapy (eg, 
cancer vaccine [including OCV-501], lymphocyte or dendric 
cell transfusional treatment) 
4) Patients who have received drugs potentially affecting the 
immune system within 4 weeks before starting IMP 
administration or who may receive such drugs after start of 
the trial (eg, corticosteroid systemic administration, 
immunosuppressants, immunostimulants, and anti-cancer 
drugs) 
5) Patients who have a history or complication of autoimmune 
diseases (eg, Hashimoto's disease, idiopathic 
thrombocytopenic purpura, autoimmune hepatitis, or 
connective tissue disease) or primary immune deficiency 
disease 
6) Patients who have active infectious diseases 
7) Patients who have a history or complication of interstitial 
pneumonia 
8) Patients who have a severe concurrent disease (eg, cardiac 
failure [NYHA class III or IV], uncontrolled diabetes mellitus, 
uncontrolled hypertension) or psychiatric illness  likely to 
interfere with participation in this trial 
9) Patients who are HIV antibody positive or HBV-DNA 
positive, or have unrecovered* chronic hepatitis C with 
positive HCV antibody 
*: Recovery is determined by sustained virologic response of 
HCV-RNA. 
10) Patients who have cirrhosis 
11) Patients who have a history of hypersensitivity or serious 
adverse drug reaction to any of the components of IMP 
12) Patients who have a concurrent second cancer (except 
carcinoma in situ, intramucosal cancers, or malignancies 
treated at least 5 years previously with no evidence of relapse) 
13) Patients who have been administered investigational drugs or 
individually imported drugs within 12 weeks before starting 
IMP 
14) Women with confirmed or suspected pregnancy, or breast-
feeding women 


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15) Patients not agreeing to take adequate contraceptive measures 
during the trial period and until 180 days (for males) or 120 
days (for females) after the last IMP administration 
16) Patients judged to be ineligible by the investigator (or 
subinvestigator) for any other reasons 
Discontinuation Criteria 
If any of the following conditions is met, the investigator or 
subinvestigator will discontinue administration of the IMP.  
1) If the patient wishes to withdraw from the trial 
2) If the investigator or subinvestigator judges that it is difficult 
to continue IMP administration due to occurrence of an 
adverse event 
3) If relapse of the primary disease (AML) is observed 
4) If a prohibited concomitant drug or therapy is used  
5) If it is later found that the patient did not to meet the 
eligibility criteria at the time of enrollment 
6) If the patient is found to be pregnant 
7) If it is not possible to administer the IMP within 21 days after 
obtaining informed consent 
8) If the investigator or subinvestigator judges that it is necessary 
to discontinue IMP administration for any another reason 
Investigational Medicinal 
Products, Dose and 
Regimen, and Treatment 
Period 
The trial will be designed as a two-arm trial with patients 
randomly assigned to one of the following treatment groups: 
 OCV-501 arm: 3 mg of OCV-501 (0.4 mL), once-weekly up 
to the 8th administration, and once every two weeks from the 
9th administration onward. 
 Placebo arm: Placebo (0.4 mL), once-weekly up to the 8th 
administration, and once every two weeks from the 9th 
administration onward. 
The IMP will be subcutaneously administered.  The 
administration site will be the axilla or inguinal region.  The IMP 
will be administered at a dose of 0.4 mL per injection site. 
 
Informed 
consent 
Screening 
period 
Treatment period 
(2 years)  
Post-treatment 
observation 
period 
 
 
 
 
 
 
● 
 
Rando
mized 
 
OCV-501 
         ● 
 
 
Placebo 
         ● 
 
 
 
 
 
 
 
Adjustment factors of allocation at the time of randomization: 


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・ Country/region (by each country/region: Japan, Republic of Korea, 
Taiwan) 
・ Age (60 to 64 years, 65 to70 years, and ≥ 71 years) 
Prohibited Concomitant 
Drugs and Therapies 
Only the IMP will be used for treating the primary disease, and 
concomitant use of the drugs (including Chinese herbal medicine) 
and therapies listed below is prohibited from the time of informed 
consent to the end of the post-treatment examination. 
 Other anti-cancer drugs, hormone therapy, antibody therapy, 
radiation therapy, thermal therapy or other anti-cancer 
therapies 
 Systemic administration of corticosteroids (equivalent to > 
10 mg/day of prednisolone for 2 weeks or longer) and 
systemic administration of drugs potentially affecting the 
immune system, including immunosuppressants and 
immunostimulants 
 G-CSF and GM-CSF 
 Topical application of corticosteroids at the IMP injection 
sites 
 Investigational drugs and individually imported drugs 
Endpoints 
[Efficacy] 
Primary endpoint: 
Disease-free survival (DFS) 
Secondary endpoints: 
 Overall survival (OS) 
 Quality of life (EORTC QLQ-C30) 
 Performance status (ECOG PS) 
 
[Safety] 
Adverse events, hematology test, blood biochemistry tests, vital 
signs (blood pressure, pulse rate, body temperature), urinalysis, 
body weight, and electrocardiogram 
[Exploratory] 
OCV-501-specific IFN-γ production, WT1-killer peptide specific 
IFN-γ production, anti-OCV-501 antibody level, and anti-WT1 


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antibody level, immunoglobulin, and WT1 mRNA 
Scheduled Duration of the 
Trial 
Sep 2013 through Dec 2017 
 


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Table of Contents 
Trial Protocol Synopsis ................................................................................. 3 
Table of Contents........................................................................................... 9 
List of Abbreviations and Definition of Terms ........................................ 16 
1 
Introduction ........................................................................................ 18 
1.1 
Background of Trial Plan .................................................................................. 18 
1.2 
Study Results and Trial Rationale ..................................................................... 19 
1.2.1 
Nonclinical Study Results .............................................................................. 19 
1.2.1.1 
Pharmacology ............................................................................................. 19 
1.2.1.2 
Safety Pharmacology .................................................................................. 20 
1.2.1.3 
Non-clinical Pharmacokinetics and Drug Metabolism ............................... 20 
1.2.1.4 
Toxicology .................................................................................................. 21 
1.2.2 
Clinical Trial Results ...................................................................................... 22 
1.2.3 
Trial Rationale ................................................................................................ 22 
2 
Trial Objectives .................................................................................. 24 
3 
Trial Plan............................................................................................. 25 
3.1 
Trial Design ...................................................................................................... 25 
3.1.1 
Screening Period............................................................................................. 25 
3.1.2 
Treatment period ............................................................................................ 25 
3.1.3 
Post-treatment observation period .................................................................. 27 
3.2 
Rationale for Trial Design................................................................................. 27 
3.3 
Endpoints .......................................................................................................... 28 
3.3.1 
Efficacy........................................................................................................... 28 
3.3.1.1 
Primary Endpoint ........................................................................................ 28 
3.3.1.2 
Secondary Endpoints .................................................................................. 28 
3.3.2 
Safety .............................................................................................................. 28 
3.3.3 
Exploratory ..................................................................................................... 28 
3.4 
Target Number of Patients ................................................................................ 29 
4 
Investigational Medicinal Products .................................................. 30 
4.1 
Test Product and Comparator ........................................................................... 30 
4.1.1 
Test Product .................................................................................................... 30 


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4.1.2 
Comparator ..................................................................................................... 31 
4.2 
Packaging and Labeling .................................................................................... 31 
4.2.1 
Packaging ....................................................................................................... 31 
4.2.2 
Contents of Label ........................................................................................... 31 
5 
Trial Population ................................................................................. 32 
5.1 
Target Disease ................................................................................................... 32 
5.2 
Inclusion Criteria............................................................................................... 32 
5.3 
Exclusion Criteria ............................................................................................. 33 
6 
Trial Design ......................................................................................... 36 
6.1 
Dose, Regimen, and Treatment Period ............................................................. 36 
6.2 
Prior and Concomitant Treatment ..................................................................... 37 
6.2.1 
Prohibited Concomitant Drugs and Therapies ............................................... 37 
6.3 
Method of Minimizing or Avoiding Bias ......................................................... 38 
7 
Trial Procedures ................................................................................. 39 
7.1 
Schedule and Procedures .................................................................................. 39 
7.1.1 
Acquisition of Informed Consent ................................................................... 43 
7.1.2 
Screening Examination .................................................................................. 43 
7.1.2.1 
Screening Examination ............................................................................... 43 
7.1.2.2 
Subject Information .................................................................................... 44 
7.1.2.3 
Allocation of Investigational Medicinal Products to Subjects at 
Enrollment (Before Week 1 IMP Administration) ..................................... 45 
7.1.3 
Observations, Examinations, and Evaluations During the Observation 
Period ............................................................................................................. 45 
7.1.3.1 
Observations, Examinations, and Evaluations From Week 1 to Week 
8 .................................................................................................................. 45 
7.1.3.1.1 
Week 1 (1st Administration [Day 1]) ...................................................... 45 
7.1.3.1.2 
Weeks 2, Week 4, Week 6, and Week 8 ................................................. 46 
7.1.3.1.3 
Week 3 and Week 7 ................................................................................ 47 
7.1.3.1.4 
Week 5 .................................................................................................... 47 
7.1.3.2 
Observations, Examinations, and Evaluations From Week 9 to Week 
104 .............................................................................................................. 48 
7.1.3.2.1 
Week 9 .................................................................................................... 48 
7.1.3.2.2 
From Week 11 to Week 104 ................................................................... 49 


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7.1.4 
Observations, Examinations, and Evaluations During the Post-
Treatment Observation Period........................................................................ 50 
7.1.4.1 
Observations, Examinations, and Evaluations at 11 to 17 days After 
Week 103 (Completion Examination) ........................................................ 50 
7.1.4.2 
Time of Withdrawal and Withdrawal Examination.................................... 51 
7.1.5 
Follow-up Investigation ................................................................................. 52 
7.1.5.1 
Adverse Events ........................................................................................... 52 
7.1.6 
Outcome Observation ..................................................................................... 52 
7.1.6.1 
Overall Survival .......................................................................................... 52 
7.1.6.2 
Post Treatment for AML............................................................................. 52 
7.2 
Method of Evaluation ....................................................................................... 53 
7.2.1 
Efficacy Evaluation ........................................................................................ 53 
7.2.1.1 
Relapse of AML Based on the Response Criteria of the International 
Working Group ........................................................................................... 53 
7.2.1.2 
Quality of Life (QOL) (The European Organization for Research and 
Treatment of Cancer [EORTC] QLQ-C30) ................................................ 54 
7.2.1.3 
Performance Status (The Eastern Cooperative Oncology Group 
performance status [ECOG PS]) ................................................................. 54 
7.2.2 
Safety Evaluation ........................................................................................... 55 
7.2.2.1 
Body Weight ............................................................................................... 55 
7.2.2.2 
Vital Signs (Body Temperature, Blood Pressure, and Pulse Rate) ............. 55 
7.2.2.3 
Clinical Laboratory Tests (Hematology test, Blood Biochemistry 
Test) and Urinalysis .................................................................................... 55 
7.2.2.4 
12-Lead Electrocardiography ...................................................................... 56 
7.2.2.5 
Medical Interview ....................................................................................... 56 
7.2.2.6 
Adverse Events ........................................................................................... 56 
7.2.2.7 
Concomitant Drug Survey .......................................................................... 56 
7.2.3 
Evaluation of Exploratory Items .................................................................... 56 
7.2.3.1 
WT1 mRNA Expression Level ................................................................... 57 
7.2.3.2 
OCV-501-Specific IFN-γ Production and WT1-killer Peptide Specific 
IFN-γ Production ........................................................................................ 57 
7.2.3.3 
Anti-OCV-501 Antibody and Anti-WT1 Antibody .................................... 57 
7.2.3.4 
Immunoglobulin ......................................................................................... 58 
7.2.4 
Evaluation of Other Items .............................................................................. 58 


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7.2.4.1 
HLA Genotyping ........................................................................................ 58 
7.2.5 
Investigational Medicinal Product Compliance ............................................. 59 
7.3 
Measures to Be Taken for Subjects Visiting or Planning to Visit Other 
Hospitals or Departments .................................................................................. 59 
8 
Adverse Events ................................................................................... 60 
8.1 
Definitions......................................................................................................... 60 
8.1.1 
Adverse Event ................................................................................................ 60 
8.1.2 
Serious Adverse Event ................................................................................... 60 
8.2 
Response to Occurrence of Adverse Events ..................................................... 61 
8.2.1 
Actions to Be Taken for Subjects ................................................................... 61 
8.2.2 
Expedited Reporting of Serious Adverse Events and Events Specified 
by the Sponsor ................................................................................................ 61 
8.2.3 
Expedited Reporting of Non-serious Adverse Events Resulting in 
Discontinuation of IMP Administration ......................................................... 63 
8.2.4 
Emergency Code Breaking (Procedure for Unblinding During the Trial 
Period) ............................................................................................................ 63 
8.3 
Assessment of Adverse Events ......................................................................... 63 
8.3.1 
Terms for Adverse Events .............................................................................. 63 
8.3.2 
Date of Onset and Recovery ........................................................................... 63 
8.3.3 
Severity ........................................................................................................... 64 
8.3.4 
Causal Relationship With Investigational Medicinal Product ....................... 64 
8.3.5 
Actions to Be Taken Regarding IMP Administration .................................... 65 
8.3.6 
Actions to Be Taken for Adverse Events ....................................................... 65 
8.3.7 
Outcome ......................................................................................................... 65 
8.4 
Follow-up Investigation of Adverse Events ...................................................... 66 
8.5 
Pregnancy .......................................................................................................... 67 
8.5.1 
Guidance to Subjects Including Contraceptive Methods ............................... 67 
8.5.2 
Actions to Be Taken by the Investigator or Subinvestigator When 
Pregnancy Is Suspected .................................................................................. 67 
8.5.3 
Actions to Be Taken by the Investigator or Subinvestigator When a 
Subject Is Discovered to Be Pregnant ............................................................ 68 
8.5.4 
Expedited Reporting of Pregnancy ................................................................. 68 
8.5.5 
Follow-up Investigation of Pregnancy ........................................................... 68 


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Withdrawal of Individual Subjects From the Trial ....................... 69 
9.1 
Screen Failure ................................................................................................... 69 
9.2 
Criteria and Procedures for Withdrawal of Individual Subjects ....................... 69 
9.3 
Follow-up Investigation of Subjects Who Do not Visit the Trial Site .............. 70 
10 
Collection of Case Report Form Data and Specification of 
Source Data ......................................................................................... 71 
10.1 
Collection of Case Report Form Data ............................................................... 71 
10.2 
Source Documents ............................................................................................ 71 
10.3 
Case Report Form Items to Be Treated as Source Data .................................... 72 
10.4 
Data to Be Collected by the Sponsor ................................................................ 72 
11 
Statistical Analysis ............................................................................. 73 
11.1 
Statistical Analysis Sets .................................................................................... 73 
11.1.1 
Safety Analysis Set (SS) ................................................................................. 73 
11.1.2 
Full Analysis Set (FAS) ................................................................................. 73 
11.1.3 
Per Protocol Set (PPS).................................................................................... 73 
11.1.4 
Immune Response Set (IRS) .......................................................................... 73 
11.2 
Handling of Data ............................................................................................... 73 
11.3 
Analysis Items and Method ............................................................................... 73 
11.3.1 
Efficacy Analysis ............................................................................................ 73 
11.3.1.1 
Primary Endpoint ........................................................................................ 74 
11.3.1.2 
Secondary Endpoints .................................................................................. 75 
11.3.2 
Safety Analysis ............................................................................................... 77 
11.3.3 
Exploratory Items Analysis ............................................................................ 77 
11.3.4 
Demographic and Other Baseline Characteristics .......................................... 78 
11.3.5 
Extent of Exposure ......................................................................................... 78 
11.3.6 
Significance Level and Confidence Interval .................................................. 79 
11.3.7 
Subgroup Analysis ......................................................................................... 79 
11.4 
Procedures for Reporting Deviations From the Original Statistical 
Analysis Plan..................................................................................................... 80 
11.5 
Rationale for Target Number of Patients .......................................................... 80 
12 
Quality Control and Quality Assurance for the Trial .................... 81 
13 
General Items of Caution Pertaining to the Trial ........................... 82 


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13.1 
Ethics and GCP Compliance ............................................................................. 82 
13.2 
Institutional Review Board ............................................................................... 82 
13.3 
Subject Consent ................................................................................................ 82 
13.3.1 
Procedures for Obtaining Consent ................................................................. 82 
13.3.2 
Contents of Informed Consent Form .............................................................. 83 
13.3.3 
Amendments to the Informed Consent Form ................................................. 84 
13.4 
Management of Investigational Medicinal Products ......................................... 84 
13.5 
Direct Access to Source Documents and Monitoring ....................................... 85 
13.5.1 
Direct Access to Source Documents .............................................................. 85 
13.5.2 
Monitoring ...................................................................................................... 85 
13.5.3 
Documents to Be Retained by the Investigator .............................................. 85 
13.6 
Deviations From and Changes or Amendments to the Trial Protocol .............. 85 
13.6.1 
Deviations From the Trial Protocol ................................................................ 85 
13.6.2 
Amendments to the Trial Protocol ................................................................. 86 
13.7 
Archiving of Records ........................................................................................ 86 
13.8 
Termination or Interruption of Part or All of the Trial ..................................... 86 
13.8.1 
Termination or Interruption of the Trial at Individual Trial Sites .................. 86 
13.8.2 
Termination or Interruption of the Entire Trial .............................................. 86 
13.9 
Protection of Subjects’ Personal Information ................................................... 87 
13.10 
Compensation for Injury to Health ................................................................... 87 
13.11 
Agreement on Publication ................................................................................. 87 
14 
Trial Administrative Structure ......................................................... 88 
15 
Scheduled Duration of the Trial ....................................................... 89 
16 
References ........................................................................................... 90 
 
Annex 1: 
Emergency Contact 
Annex 2: 
Trial Organization  
Annex 3: 
Volume of Blood Sampling 
 
 


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List of Abbreviations and Definition of Terms 
List of Abbreviations 
Abbreviation 
Expansion 
AE 
Adverse event 
AML 
Acute myeloid leukemia 
APL 
Acute promyelocytic leukemia  
CR 
Complete remission 
Cr 
Creatinine 
CRO 
Contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTL 
Cytotoxic T lymphocyte 
DFS 
Disease-free survival 
DLT 
Dose limiting toxicity 
DTH 
Delayed-type hypersensitivity 
ECG 
Electrocardiography  
ECOG 
Eastern Cooperative Oncology Group 
EDC 
Electronic data capture 
EORTC 
QLQ-C30 
The European Organization for Research and Treatment of Cancer QLQ-C30 
FAS  
Full analysis set 
FDA 
Food and Drug Administration  
G-CSF 
Granulocyte colony-stimulating factor 
GM-CSF 
Granulocyte macrophage colony-stimulating factor 
GVL 
Graft versus leukemia 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
IMP 
Investigational medicinal product 
IVRS 
Interactive Voice Response Services 
IWRS 
Interactive Web Response Services 
HR 
Hazard ratio 
LOCF 
Last observation carried forward 
MDS 
Myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities (The ICH international medical 
dictionary) 
MG 
May-Giemsa 
MRD 
Minimal residual disease 
NYHA 
New York Heart Association 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
QOL 
Quality of life 
PPS 
Per protocol set 


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Abbreviation 
Expansion 
PS 
Performance status 
QTc 
Corrected QT interval 
QTcF 
QT interval as corrected by Fridericia’s formula 
RFS 
Relapse-free survival 
SS 
Safety Set 
Th1 
Type I helper T lymphocytes 
ULN 
Upper limit of normal 
WG 
Wright’s-Giemsa 
WT1 
Wilm’s tumor gene 1 
 
Definitions of Terms 
Term 
Definition 
Screen failure 
A screen failure is a subject from whom written informed consent was 
obtained, but to whom an investigational medicinal product (IMP) 
was not allocated 
Individual subject 
trial start date 
The day of obtaining the subject’s written informed consent 
Individual subject 
withdrawal 
A subject who discontinue OCV-501 or placebo treatment before 
completion of the post-treatment observation period 
Individual subject 
trial withdrawal date 
The day of the withdrawal examination of the post-treatment 
observation period within 7 days after the investigator or 
subinvestigator judged withdrawal to be necessary 
Individual subject 
completion 
A subject who completes 2 years of treatment with OCV-501 or 
placebo, and completes the post-treatment examination at 11-17 days 
after the end of IMP administration 
Individual subject 
trial completion date 
The day of the completion examination at 11-17 days after the end of 
the 2-year IMP administration period 
Individual subject 
trial period 
The period from the day of obtaining the subject’s informed consent 
to the day of trial completion or the day of the withdrawal 
examination.  Does not include the follow-up period nor the outcome 
survey. 
 
 


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1 
Introduction  
1.1 
Background of Trial Plan 
Acute myeloid leukemia (AML) is a malignant disease derived from myeloid 
hematopoietic cells.  In AML, unregulated proliferation of leukemia cells is associated 
with inhibition of normal hematopoiesis.  AML is a life-threatening disease with various 
symptoms such as infection, anemia, hemorrhage due to thrombocytopenia, and organ 
disorders.  Although AML occurs in people of all ages, it is known to be more prevalent 
among the elderly, and the median age of onset is reported to be 62 years in Japan.1  
Treatment of AML is based on the concept of total cell kill.  Normally, after complete 
remission (CR) is achieved by remission induction therapy to reduce leukemia cell count 
to below 109 cells, consolidation therapy is performed to further reduce the number of 
residual leukemia cells to near zero.2  However, it is not rare for patients, especially 
elderly patients, to experience relapse due to proliferation of residual leukemia cells after 
CR.  The prognosis for AML becomes worse as age increases.  There are many reasons 
for this.  For one, the deterioration in organ functions (including bone marrow, liver, 
cardiorespiratory and renal functions) in the elderly constitutes a barrier to adequate AML 
therapy.  Also, AML in elderly patients more frequently arises from antecedent 
hematologic disorders such as myelodysplastic syndrome (MDS), which is always 
associated with a worse outcome.  Moreover, elderly AML patients have a higher 
incidence of poor-risk cytogenetics, which is associated with poor outcome.  In an 
investigation involving elderly AML patients (aged 50 to 70 years) not receiving 
allogeneic hematopoietic cell transplantation, even for those patients who achieved CR, 
the 3-year relapse-free survival (RFS) was as low as 29% and many patients experienced 
relapse.3  When treating elderly patients with antitumor drugs, it may be necessary to 
reduce the dose.  There are a considerable number of limitations and much debate 
regarding therapeutic regimens in elderly patients with leukemia.  Therefore, a new 
therapy is needed to prevent relapse of AML, and extend survival of elderly patients with 
AML. 
In recent years, investigations have been made into cancer immunotherapy using tumor-
specific antigen peptide as a new treatment for cancers, including AML.  Tumor-specific 
antigen peptides are classified as either killer peptide or helper peptide.  Killer peptide 
directly increases cytotoxic T lymphocyte (CTL) count via HLA class I molecules.  
Helper peptide indirectly increases CTL count by activating Th1 cells via HLA class II 
molecules.  The WT1 gene was isolated as the causal gene of Wilms’ tumor, a cancer of 


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the kidney typically occurring in children,4,5 and it was initially categorized as a tumor 
suppressor gene.6,7  Although WT1 gene is also seen localized in normal tissues such as 
genitalia, kidneys, hematopoietic progenitor cells, and mesothelial tissues,8,9 further study 
has revealed an overexpression of WT1 in various types of solid tumors and 
hematological malignancies,10,11,12,13 and also an oncogene-like role.14,15  
OCV-501, an HLA class II-restricted WT1 helper peptide licensed from International 
Institute of Cancer Immunology, Inc., consists of 16 amino acid residues derived from the 
WT1 gene product protein.  In in vitro studies, OCV-501 not only induced or activated 
various HLA class II-restricted OCV-501-specific Th1 cells, but also increased the 
induction of WT1-specific CTLs, suggesting that it is a promising peptide for use in 
cancer immunotherapy.16,17   
1.2 
Study Results and Trial Rationale   
1.2.1 
Nonclinical Study Results 
1.2.1.1 
Pharmacology 
OCV-501 significantly induced OCV-501-specific type 1 T-helper (Th1) cells and 
cytotoxic T-lymphocytes (CTLs) in peripheral blood mononuclear cells (PBMCs) from 
healthy adult donors.  OCV-501 also significantly induced interferon gamma (IFN-γ) 
production from the OCV-501-specific T-cells in a dose-dependent manner.  In some 
cases, the IFN-γ production induced by OCV-501 was inhibited by addition of anti-
human leukocyte antigen (HLA)-DR antibody, but no inhibition by anti-HLA-DQ 
antibody was seen.  OCV-501 also showed binding to and/or activation of T-cell via the 
HLA class II molecules HLA-DRB1*01:01, DRB1*04:05, DRB1*08:02, DRB1*08:03, 
DRB1*09:01, DRB1*13:02, DRB1*14:03, DRB1*14:05, DRB1*15:01, DRB1*15:02, 
DRB3*02:02, DRB4*01:01, DQB1*04:01, DPB1*05:01, and DPB1*09:01.  As one 
possible mechanism of OCV-501’s antitumor effect, OCV-501 increased the number of 
HLA-A*02:01-restricted WT1-derived killer peptide WT1-126-134 (WT1-126)-specific 
CTLs in 3 of 3 samples and the number of HLA-A*24:02-restricted WT1-derived 
modified killer peptide WT1-235-243 (WT1-235mu)-specific CTLs in 6 of 8 samples in 
the presence of PBMC-derived OCV-501-specific Th1 cells and WT1-killer peptide-
specific CTLs.  Additionally, 18 of 20 OCV-501-specific Th1 clones displayed 
significant cytolytic activity. 


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1.2.1.2 
Safety Pharmacology 
The effects of OCV-501 on general physical condition and behavior were evaluated by 
modified Irwin’s method and effects on the respiratory system were evaluated by whole 
body plethysmography as part of a single subcutaneous dose toxicity study in rats.  
Effects on blood pressure, heart rate, and electrocardiography (ECG) were evaluated as 
part of a single subcutaneous dose toxicity study in dogs.  In addition, effects on blood 
pressure, heart rate, and ECG were also evaluated as a part of intermittent subcutaneous 
dose toxicity studies in dogs.  No effects on any parameters were observed at a dose of 
4.5 mg/kg in the single-dose toxicity studies and at doses of up to 2.5 mg/kg in the 
intermittent-dose toxicity studies. 
Effects on human ether-a-go-go related gene (hERG) currents were not investigated in an 
in vitro study because the administration route for OCV-501 is subcutaneous, for which 
systemic exposure is low.  Furthermore, effects on ECG were sufficiently evaluated as 
described above in single- and intermittent-dose studies in dogs and no specific issues 
were identified that would pose notable risk in AML patients in clinical trials. 
1.2.1.3 
Non-clinical Pharmacokinetics and Drug Metabolism 
OCV-501 was administered subcutaneously at single doses of 0.45, 1.5, and 4.5 mg/kg to 
fed male rats and at a single dose of 1.5 mg/kg to fed female rats, intradermally at a single 
dose of 1.5 mg/kg to fed male rats, and intravenously at a single dose of 1.5 mg/kg to fed 
male rats.  Following subcutaneous and intradermal administration, the plasma 
concentration of OCV-501 was below the lower limit of quantification (LLOQ, 5 ng/mL) 
at up to 24 hours postdose.  Following intravenous administration, the plasma 
concentration of OCV-501 was below the LLOQ (5 ng/mL) at up to 6 hours postdose. 
OCV-501 was administered subcutaneously at single doses of 0.45, 1.5, and 4.5 mg/kg 
and intravenously at a single dose of 1.5 mg/kg to fed male beagle dogs.  Following 
subcutaneous administration, one animal at a dose 4.5 mg/kg showed a plasma 
concentration of 12.69 ng/mL at 0.5 hours postdose and 20.21 ng/mL at 1 hour postdose.  
Following intravenous administration, the plasma concentration in one animal was 
8.211 ng/mL at 0.083 hours postdose. 
In investigation of the in vitro stability of OCV-501 in fresh rat, dog, and human plasma 
at 37°C, the half-life (t1/2) of OCV-501 was respectively 9.90, 4.15, and 2.30 minutes.  
Following incubation of OCV-501 (250 μg/mL) in cryopreserved rat, dog, and human 
plasma at 37°C for 20 minutes, 4 metabolites were detected in the rat and dog plasma and 
5 metabolites were detected in human plasma. 


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1.2.1.4 
Toxicology  
Single-dose Toxicity:  Single subcutaneous dose toxicity studies in rats and dogs showed 
no systemic toxicity, and the approximate lethal dose was judged to be higher than 
4.5 mg/kg. 
Intermittent-dose Toxicity:  In 4-week intermittent (once weekly) subcutaneous dose 
toxicity studies in rats and dogs with 4-week recovery tests, the no observed adverse 
effect level (NOAEL) for systemic toxicity was estimated to be 2.5 mg/kg in both species.  
As local changes at the administration site, large or small cavity, hemorrhage, edema, 
fibrosis, granuloma, inflammatory cell infiltration and monocyte infiltration were 
commonly observed in both the vehicle control group administrated a mixture of 
Montanide and saline without OCV-501 and the OCV-501-treated groups, and it was 
considered that these changes were mainly attributable to the irritancy of Montanide used 
as an adjuvant.  The changes at the administration site showed gradual recovery over time 
in both the vehicle control group and the OCV-501-treated groups.  In subsequent 13-
week intermittent (once weekly) subcutaneous dose toxicity studies in rats and dogs with 
4-week recovery tests, the NOAEL for systemic toxicity was again estimated to be 2.5 
mg/kg in both species, and the changes at the administration site were similar to those 
observed in the 4-week intermittent dose toxicity studies, showing no increase in severity 
with prolongation of the dosing period. 
Genotoxicity:  The genotoxicity studies routinely conducted for pharmaceuticals are not 
applicable to OCV-501, which is a synthetic peptide, and therefore genotoxicity was not 
investigated. 
Local Irritancy:  The local irritation potential of OCV-501 emulsion for injection at the 
intended clinical route was evaluated in intermittent subcutaneous dose toxicity studies in 
rats and dogs.  In addition to those studies, the irritation potential of OCV-501 emulsion 
for injection was investigated by single intradermal administration in rabbits, since it was 
considered possible that the intradermal route might also be used for clinical 
administration of OCV-501 emulsion.  Results showed irritant reactions such as 
acanthosis, hemorrhage, crust, erosion, pseudoeosinophil infiltration, and histiocyte 
infiltration at the administration site for each OCV-501 emulsion for injection (0%, 
0.025%, 0.075%, 0.25%, and 0.75%), as well as for 0% formulation (mixture of 
Montanide and saline).  Some of these changes showed increased frequency or severity at 
sites treated with 0.25% and 0.75% emulsions for injection compared with the 0% 
formulation.  However, there were only slight differences in any of the findings between 
OCV-501 emulsions for injection and the 0% formulation.  It was therefore considered 


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that the changes at the administration site were mainly attributable to the irritancy of 
Montanide used as an adjuvant. 
1.2.2 
Clinical Trial Results 
Trial 311-10-001 (Japan) was a phase 1 trial of OCV-501 to assess the safety and 
tolerability of OCV-501 subcutaneously administered once a week for 4 weeks at doses 
of 0.3, 1, and 3 mg in elderly patients with AML who had completed standard 
consolidation therapy after being judged to have achieved complete remission following 
an induction regimen.  Of 9 subjects enrolled (3 subjects in each cohort: 0.3, 1, and 3 mg), 
no subject showed relapse after administration of OCV-501.  No dose limiting toxicity 
(DLT) was observed in any of the 3 cohorts, and the maximum tolerated dose was 
therefore considered to be ≥ 3 mg.  There was no evidence of major safety problems in 
any cohort.  In OCV-501-specific delayed-type hypersensitivity reaction (DTH) 
observation, erythema was observed in all 3 cohorts and induration was observed in one 
subject each in the 0.3 mg and 3 mg cohorts. 
Trial 311-10-002 is ongoing as of the cutoff date (7 May 2013).  Trial 311-10-002 is a 
long-term, open-labeled extension trial to assess the safety of OCV-501 administered 
once a week in patients with AML who completed Trial 311-10-001 and who desired to 
continue receiving OCV-50118,19.  Aggravation of the underlying disease (AML) was 
reported in 5 subjects (5 incidences) as SAEs, and all of these events were judged by the 
investigator to be unrelated to the IMP.  Drug allergy was reported in one subject, and the 
event was not judged by the investigator to be an SAE, although the sponsor considered it 
to be serious. 
1.2.3 
Trial Rationale 
OCV-501 is a drug product containing an HLA class II restricted WT1 derived peptide.  
In in vitro pharmacology studies, OCV-501 has demonstrated significant induction of 
OCV-501-specific Th1 cells and CTLs in PBMC from healthy adult donors,20 and 
significant induction of interferon (IFN-γ) production from OCV-501-specific T cells in a 
dose-dependent manner.  The activation effect on OCV-501-specific T cells was HLA 
class II restricted.20,21  In the presence of OCV-501-specific T cells, the addition of OCV-
501 increased the number of co-existing WT1 killer peptide-specific CTLs.22  
Because WT1 expresses frequently in patients with AML11,12,23 and AML patients often 
show an increased number of WT1-specific CTLs in comparison with healthy donors,24 
OCV-501 is being developed as an AML therapy product.  It is expected that normal 


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leucocytes will have recovered and there will be fewer leukemia cells in patients who 
have completed consolidation therapy.  Therefore, AML patients who have completed 
consolidation therapy were set as the target trial subjects. 
In the phase 1 trial (Trial 311-10-001), OCV-501 was subcutaneously administered once 
a week for 4 times at doses of 0.3 mg, 1 mg, and 3 mg in elderly AML patients and safety 
and tolerability of OCV-501 were assessed.  In this phase 1 trial, no DLTs were reported 
and the tolerability of OCV-501 treatment up to a dose of 3 mg was confirmed.  In 
addition, OCV-501 specific DTH was observed at each dose.  This finding suggests that 
OCV-501 induces the T cell mediated immune response.  See Section 3.2, for the 
rationale of setting the trial design, dose, regimen, and primary endpoint. 
This trial is planned as a randomized placebo-controlled comparative trial, to assess the 
efficacy and safety of OCV-501 treatment as a maintenance therapy in elderly patients 
with AML who have completed consolidation therapy after being judged to have 
achieved CR following an induction regimen.  In the ongoing phase 1 extension trial 
(Trial 311-10-002), drug allergy was observed for one patient and it was considered that a 
causal relationship between the adverse event (AE) and OCV-501 could not be ruled out.  
Therefore, in this phase 2 trial, patients’ general conditions, including injection site 
reaction, will have to be observed at the trial site for one hour after IMP administration. 
Based on the above, the conduct of this clinical trial, as described in this clinical trial 
protocol, was considered to be scientifically and ethically justified. 
See the investigator’s brochure for further details of data mentioned in this protocol 
and other trial results. 
 
 
 
 
 


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2 
Trial Objectives 
Primary objective  
The primary objective of this trial is to compare disease-free survival (DFS) in patients 60 
years or older with AML who are randomly assigned to receive either OCV-501 
monotherapy or placebo. 
Secondary objectives 
The secondary objectives of this trial are:  
 to compare overall survival between both treatment arms 
 to compare patient quality of life (QOL; The European Organization for Research and 
Treatment of Cancer [EORTC] QLQ-C30) and performance status (ECOG PS) 
between both treatment arms 
 to characterize and compare safety in the both treatment arms 
 to assess immunological responses:  
OCV-501-specific IFN-γ production, WT1-killer peptide specific IFN-γ production, 
anti-OCV-501 antibody level, anti-WT1 antibody level, and immunoglobulin level 
 to assess WT1 mRNA level 
 
 
 
 
 
 
 
 
 
 
 
 
 


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3 
Trial Plan 
3.1 
Trial Design 
This trial is a multinational, multicenter, randomized, double-blind, placebo-controlled 
trial in elderly patients with AML, to compare DFS in patients 60 years or older with 
AML who are randomly assigned to receive either OCV-501 monotherapy or placebo. 
This trial consists of the following three periods. 
3.1.1 
Screening Period  
The investigator or subinvestigator will obtain written consent directly from potential 
subjects prior to the screening examination.  Within 3 weeks before IMP administration, 
bone marrow aspiration and hematology tests will be performed to confirm the 
continuation of CR.  Virus test, chest x-ray, hCG pregnancy test, body height, and PS will 
be evaluated. A medical interview, blood biochemistry tests, urinalysis, vital signs, body 
weight, electrocardiogram, AE observation, and a concomitant drug survey will be 
performed in the screening period.   
The eligible patients will be randomly assigned to one of following treatment groups at a 
ratio of 1:1: 
 OCV-501 arm: 3 mg of OCV-501 (0.4 mL)  
 Placebo arm: Placebo (0.4 mL)  
The patients will be assigned to either treatment group via the Interactive Voice Response 
Services (IVRS) or the Interactive Web Response Services (IWRS). 
Blood sample collection for HLA genotyping, QOL (EORTC QLQ-C30) and 
measurement of WT1 mRNA expression level, OCV-501-specific IFN-γ production, 
WT1-killer peptide specific IFN-γ production, anti-OCV-501 antibody, anti-WT1 
antibody, and immunoglobulin will be performed before IMP administration of Day 1. 
3.1.2 
Treatment period 
From Week 1 to Week 104, the IMP will be subcutaneously administered once weekly up 
to the 8th administration, and every two weeks from the 9th administration onward.  The 
subject’s general conditions, including injection site reaction, must be observed at the 
trial site for one hour after IMP administration, because drug allergy was reported in 
another trial (Trial 311-10-002) using OCV-501 and it was considered that a causal 
relationship with OCV-501 could not be ruled out, and the AE was considered to be 
serious by the sponsor.  Hematology tests will be performed at least once every two 


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weeks.  If leukemic blast cells appear in peripheral blood or if there is a reduction in 
blood cell components, bone marrow aspiration will be performed.  Smears will be 
prepared after hematology tests and bone marrow aspiration at every time point, and 
smears will be collected by the sponsor for central pathological review.  Blood sampling 
for measurement of WT1 mRNA expression level, anti-OCV-501 antibody, anti-WT1 
antibody, and immunoglobulin will be performed at least once every four weeks.  OCV-
501-specific IFN-γ production, WT1-killer peptide specific IFN-γ production will be 
assessed at Week 5, Week 9, Week 13, and every 12 weeks.  QOL and PS will be 
measured at least once every 4 weeks.  A concomitant drug survey will be performed at 
every scheduled visit.  For the safety of the subjects, a medical interview, blood 
biochemical tests, urinalysis, and AE observation will be performed.  Vital signs, body 
weight, and 12-lead ECG will be measured.  
Central Pathological Review 
Trial sites will prepare extra smears, other than for evaluation at the trial site, from bone 
marrow and peripheral blood in all scheduled tests performed during the trial, and prepare 
a May-Giemsa (MG) staining* or Wright’s-Giemsa (WG) staining* sample (to protect 
subjects’ personal information, only subject numbers and the name of the staining method 
will be written on smears).  The sponsor will collect the smears prepared during the trial 
(from screening period to post-treatment observation period).  Retrospective evaluation of 
samples will be conducted by the central pathological review committee.  The central 
pathological review committee will evaluate the sample used at the judgment of relapse 
by the trial site and the previous sample from before relapse, and verify the judgment of 
relapse of the trial site.  (If possible, the trial site will prepare a peroxidase-stained smear, 
a specific esterase-stained smear, and a nonspecific esterase-stained [α-naphthyl-butyrate-
esterase-stained and/or α-naphthyl-acetate-esterase-stained] smear from bone marrow and 
submit them to the sponsor when relapse has been judged at the trial site.) 
* Both staining methods are acceptable, but only one method may be used for each 
subject. 
If a subject does not show relapse at the completion examination, or if a patient 
discontinues treatment for any reason other than relapse, the central pathological review 
committee will evaluate samples from the completion examination or withdrawal 
examination and confirm that the patient has not relapsed.   


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3.1.3 
Post-treatment observation period 
Subjects will return to the trial site 11 to17 days after the last dose of the 2-year IMP 
administration period to undergo a completion examination during the post-treatment 
observation period.  If a patient discontinues IMP administration before completion of the 
2-year treatment period, the patient will undergo a withdrawal examination within 7 days 
after the investigator or subinvestigator judged withdrawal to be necessary.  
3.2 
Rationale for Trial Design 
In this trial, the primary endpoint is DFS defined as the time from randomization to AML 
relapse or death from any cause, whichever comes first within the observation period.  
This endpoint was set to assess the efficacy of OCV-501 as a maintenance therapy in 
AML patients who were judged to have achieved CR following an induction regimen.  
Since DFS is a time-to-event variable, this trial was designed as a randomized 
comparative study with two treatment arms (the OCV-501 arm and the placebo-control 
arm).  No DLTs were reported and the tolerability of OCV-501 treatment up to a dose of 
3 mg was confirmed, and OCV-501 specific DTH was observed at each dose in this phase 
1 trial (Trial 311-10-001), and the number of AML patients is not very high.  The 
maximum dose (OCV-501 3 mg) that has been confirmed safe in the phase 1 trials will be 
used to assess the efficacy and safety of OCV-501 compared with placebo.  Since no 
treatments are administered in patients who complete consolidation therapy, placebo was 
set as a control. 
The DFS rates in maintenance therapy with other drugs25,26,27 in AML patients 60 years 
or older are summarized below.  As DFS rates were approximately 10 to 30% after 2 
years, approximately 70 to 90% of events could be observed within 2 years.  Thus, the 
observation period of DFS in this trial is set from the time of randomization to 2 years 
after the first IMP administration.   
Disease Free Survival Rates 
Publication 
1 year later 
2 years later  
3 years later 
Cancer and Leukemia Group B Study 9720 (2008)25 
29% 
10% 
5% 
Hellstrand et al (2008)26,* 
44% 
32% 
27% 
Cancer and Leukemia Group B study 9420 (2002)27,** 
40% 
20% 
18% 
Note: values are round number 
*Leukemia-free survival: Definition is identical to DFS.  Values are estimated by comparing data among 
all patients and patients less than 60 years of age. 
** Results of Interleukin 2 monotherapy 
 


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For overall survival (OS), the cutoff date was set as the date after 728 days (2 years) from 
the day that the last subject started IMP administration  
As mentioned above, no DLTs were reported and the tolerability of OCV-501 treatment 
up to a dose of 3 mg was confirmed, and OCV-501 specific DTH was observed at each 
dose in the phase 1 trial.  This study will consist of two arms (ie, OCV-501 arm and 
placebo arm) with consideration of feasibility of patient enrollment.  
Once-weekly dosing was set as the administration method because the safety of this 
administration method was confirmed in the phase 1 trial.  Considering that other cancer 
treatment vaccines were administered 6 to 12 times weekly28 29 30 31 or once every two 
weeks,32 33 the IMP will be administered once a week until the 8th administration and 
will be administered once every two weeks from the 9th administration onward.  The IMP 
will be administered subcutaneously in the same manner as in the phase 1 trial. 
This study protocol was developed based on the results of consultation with the 
Pharmaceuticals and Medical Devices Agency (PMDA, the regulatory agency of Japan). 
3.3 
Endpoints 
3.3.1 
Efficacy 
3.3.1.1 
Primary Endpoint 
Disease-free survival (DFS) 
3.3.1.2 
Secondary Endpoints 
 Overall survival (OS) 
 Quality of life (EORTC QLQ-C30) 
 Performance status (ECOG PS) 
3.3.2 
Safety 
Adverse events, hematology test, blood biochemistry tests, urinalysis, vital signs (blood 
pressure, pulse rate, body temperature), body weight, and electrocardiogram 
3.3.3 
Exploratory 
 OCV-501-specific IFN-γ production, WT1-killer peptide specific IFN-γ production, 
anti-OCV-501 antibody level, anti-WT1 antibody level and immunoglobulin 
 WT1 mRNA level 
 
[Rationale for endpoint selection] 


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[Efficacy] 
Primary endpoint  
This trial was planned to assess the contribution of OCV-501 to life prognosis 
through relapse prevention in AML patients who have completed consolidation 
therapy.  Therefore, disease-free survival (DFS:  time from randomization to AML 
relapse or death from any cause, whichever comes first, within the observation 
period) was set as the primary endpoint. 
Secondary Endpoints 
Overall survival (OS) was set as a general endpoint relevant to survival in anticancer 
drug therapy.  The representative QOL and performance status surveys, EORTC 
QLQ-C30 and ECOG PS, were set to assess QOL and PS in subjects. 
[Safety] 
General tests were set out of consideration for subjects’ safety and to assess the safety 
of OCV-501.  
[Exploratory] 
Measurements of OCV-501-specific IFN-γ production and WT1-killer peptide 
specific IFN-γ production were set to measure the helper T cell activation and WT1-
killer specific T cell activation induced by OCV-501.  Measurements of anti-OCV-
501 antibody level and anti-WT1 antibody level were set to confirm antibody 
induction ability because antibody induction against the WT1 protein has been 
reported.34  Immunoglobulin was set to monitor whole immunological changes.  
Expressed level of WT1 mRNA was set because it is considered to be useful as a 
monitoring marker of minimal residual disease (MRD).  
 
3.4 
Target Number of Patients 
The planned number of patients is 120 in total (60 patients in the OCV-501 arm and 
60 patients in placebo arm). 


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4 
Investigational Medicinal Products 
4.1 
Test Product and Comparator 
4.1.1 
Test Product 
Code Name 
OCV-501 
Generic Name 
None 
Molecular Formula 
C94H150N32O21S 
Content and Formulation OCV-501 for injection is a subcutaneous injection formulation 
that consists of two vials, one of OCV-501 aqueous solution and 
one of emulsifier, to be mixed prior to use. 
OCV-501 aqueous solution for injection 3 mg contains OCV-501.  
The other components are citric acid monohydrate, sodium 
chloride, sodium hydroxide, glacial acetic acid and water for 
injection.   
The emulsifier contains Montanide ISA 51 VG (Montanide).   
Storage Conditions 
The IMP should be stored under conditions specified in the IMP 
label. 
 
 
 
 
 
 
 
 
 
 
 
 


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4.1.2 
Comparator  
Code Name 
Placebo 
Generic Name 
Not applicable 
Molecular Formula 
Not applicable 
Content and Formulation The placebo injection is a subcutaneous injection formulation that 
consists of two vials, one of placebo aqueous solution and one of 
emulsifier, to be mixed prior to use. 
Placebo aqueous solution for injection includes citric acid hydrate, 
sodium chloride, glacial acetic acid, sodium hydroxide and water 
for injection. 
The emulsifier contains Montanide. 
Storage Conditions 
The IMP should be stored under conditions specified in the IMP 
label. 
 
4.2 
Packaging and Labeling 
4.2.1 
Packaging 
The vial of aqueous solution of OCV-501 or placebo is packed in one box, and the vial of 
emulsifier is packed in another box. 
4.2.2 
Contents of Label 
The following information is written on the labels of IMP(s):  specification that the drug 
is for use in a clinical trial, the code name of the IMP, lot number, expiration date, storage 
conditions, name and address of the sponsor, etc. 
 


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5 
Trial Population 
5.1 
Target Disease 
Acute myeloid leukemia 
5.2 
Inclusion Criteria 
Patients who meet all of the following criteria at the time of enrollment will be selected. 
1) Patients with AML (WHO classification 2008) patients who achieved first complete 
remission within one or two courses of standard induction therapy*, and completed 
standard consolidation therapy* (one or more courses). 
* Induction therapy and consolidation therapy are according to the institution's standard of care.  
 Applicable types of disease for this trial in WHO classification 
 AML with recurrent genetic abnormalities 
 AML, myelodysplasia-related changes 
 AML, not otherwise specified 
2) Patients who are 60 years or older at the time of providing informed consent  
3) Sex: Male or female 
4) Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 
0 - 2 at the time of trial enrollment  
5) Patients with no significant impairments in the functions of major organs (as 
indicated by laboratory values) meeting the following criteria within 3 weeks of IMP 
administration:  
 Hematological functions  
Patients must not require administration of a blood-derived product or blood 
transfusion, or granulocyte colony-stimulating factor (G-CSF), granulocyte 
macrophage colony-stimulating factor (GM-CSF) 
 Neutrophil count: > 1,000/μL  
 Platelet count: > 50,000/μL 
 Hepatic functions  
 AST and ALT: < 5 × the upper limit of normal (ULN) 
 Total bilirubin: < 3 × ULN 
 Renal function 
 Serum creatinine: < 3 × ULN 
6) Patients with a life expectancy of at least 3 months   
7) Patients who have provided written informed consent within 90 days from the last 
dose of consolidation therapy on an informed consent form that has been approved by 
an institutional review board or independent ethics committee.  


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[Rationale for Inclusion Criteria] 
1) The WHO classification is used for the definition of AML and corresponding 
types of disease are specified.  
Elderly AML patients with therapy-related myeloid neoplasms have an especially 
poor prognosis and it is expected that AML will relapse at an early point in those 
patients.  Considering the pharmacological profile of OCV-501 that exerts 
therapeutic efficiency through boosting immune response, patients with therapy-
related myeloid neoplasms were excluded. 
Patients who have not achieved CR within 2 courses of induction therapy are 
considered to be poor responders and will receive salvage therapy.  Therefore, 
trial subjects were defined as patients who had achieved CR within 2 courses of 
induction therapy. 
2) Elderly AML patients were defined as patients 60 years of age or older.  There is 
no clear definition for elderly AML patients.  Patients less than 60 years of age are 
treated as younger adults in the clinical trials conducted outside Japan.  In Japan, 
patients less than 65 years of age receive strong induction therapy, the same as 
younger adults.  Since this is a multinational trial, subjects to be enrolled in the 
trial were defined as patients 60 years of age or older.  
3) This criterion was set because no differences in safety and efficacy were reported.  
4) This criterion was set because outpatients were expected for this trial.  Patients 
with PS of 2 or higher who can walk and are self-sufficing are eligible.  
5) This criterion was set to ensure patient safety.  
6) This criterion was set to ensure patient safety and to avoid any influence on 
efficacy.  
7) This criterion was set so that all subjects will start OCV-501 therapy within a 
standard period after completion of consolidation therapy, and was also set for 
regulatory reasons.  
 
5.3 
Exclusion Criteria 
Patients who fall under any of the following exclusion criteria at the time of enrollment 
will be excluded from participation in the trial. 
1) Patients who have acute promyelocytic leukemia (APL) with t(15;17)(q22;q12), 
(PML/RARA) karyotype abnormalities, and other variant types 
2) Patients who are scheduled for hematopoietic stem cell transplantation 
3) Patients who have undergone cancer immunotherapy (eg, cancer vaccine [including 
OCV-501], lymphocyte or dendric cell transfusional treatment)  
4) Patients who have received drugs potentially affecting the immune system within 4 
weeks before starting IMP administration or who may receive such drugs after start of 


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the trial (eg, corticosteroid systemic administration, immunosuppressants, 
immunostimulants and anti-cancer drugs)  
5) Patients who have a history or complication of autoimmune diseases (eg, Hashimoto's 
disease, idiopathic thrombocytopenic purpura, autoimmune hepatitis, or connective 
tissue disease) or primary immune deficiency disease 
6) Patients who have active infectious diseases 
7) Patients who have a history or complication of interstitial pneumonia 
8) Patients who have a severe concurrent disease (eg, cardiac failure [NYHA class III or 
IV], uncontrolled diabetes mellitus, uncontrolled hypertension) or psychiatric illness 
likely to interfere with participation in this trial 
9) Patients who are HIV antibody positive or HBV-DNA positive, or have unrecovered* 
chronic hepatitis C with positive HCV antibody 
*: Recovery is determined by sustained virologic response of HCV-RNA. 
10) Patients who have cirrhosis 
11) Patients who have a history of hypersensitivity or serious adverse drug reaction to any 
of the components of IMP 
12) Patients who have a concurrent second cancer (except carcinoma in situ, intramucosal 
cancers, or malignancies treated at least 5 years previously with no evidence of 
relapse)  
13) Patients who have been administered investigational drugs or individually imported 
drugs within 12 weeks before starting IMP 
14) Women with confirmed or suspected pregnancy, or breast-feeding women 
15) Patients not agreeing to take adequate contraceptive measures during the trial period 
and until 180 days (for males) or 120 days (for females) after the last IMP 
administration 
16) Patients judged to be ineligible by the investigator (or subinvestigator) for any other 
reasons 
 
[Rationale for Exclusion Criteria] 
1)  Since a high remission rate is expected with all-trans retinoic acid (ATRA) or 
arsenic trioxide therapy in patients with APL with t(15;17)(q22;q12) or its variant 
types.  Therefore, patients with APL with t(15;17)(q22;q12) or its variant types are 
excluded from the trial. 
2)  This criterion was set to exclude patients who plan to receive existing aggressive 
therapy. 
3), 4) These criteria were set to avoid any influence on efficacy evaluation. 
5) - 12) These criteria were set in consideration of the safety of subjects and to avoid 
any influence on efficacy evaluation. 
13) This criterion was set to avoid any influence on efficacy and safety evaluation. 
14), 15) These criteria were set because the safety of OCV-501 in regard to 


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reproductive potential and offspring has not been established. 
16) This criterion was set to enable the investigator or subinvestigator to consider 
factors other than the exclusion criteria in subject selection. 


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6 
Trial Design 
6.1 
Dose, Regimen, and Treatment Period 
This is a two-arm, multi-centre, phase 2 trial with patients randomly assigned to one of 
the following treatment groups: 
 OCV-501 arm:  3 mg of OCV-501 (0.4 mL) once-weekly up to the 8th 
administration, every two weeks from the 9th administration onward 
 Placebo arm:  Placebo (0.4 mL) once-weekly up to the 8th administration, 
every two weeks from the 9th administration onward 
 
The IMP will be subcutaneously administered.  The administration site will be the axilla 
or inguinal region.  The IMP will be administered at a dose of 0.4 mL per injection site. 
 
The outline of the trial plan is shown in Figure 6.1-1. 
Informed 
consent 
Screening 
period 
Treatment period 
(2 years)  
Post-treatment 
observation 
period 
 
 
 
 
 
 
● 
 
Randomized 
 
OCV-501 
         ● 
 
 
Placebo 
         ● 
 
 
 
 
 
 
  
 
Figure 6.1-1 
Trial Design 
 
Adjustment factors of allocation at the time of randomization: 
 
Country/region (by each country/region: Japan, Republic of Korea, Taiwan) 
 
Age (60 to 64 years, 65 to 70 years, and  ≥ 71 years) 
 
[Rationale for dose, regimen, and treatment period] 
  [Dose] 
In this phase 1 trial, no DLTs were reported and the tolerability of OCV-501 
treatment up to a dose of 3 mg was confirmed.30  Therefore, in consideration of 
subject safety, and the feasibility of patient enrollment in the trial (given the small 
number of AML patients), and considering that immunological response was 
observed at each dose level, the dose for this trial was set to the maximum dose 


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(OCV-501 3 mg) whose safety was confirmed in the phase 1 trial, to assess the 
efficacy and safety of OCV-501 compared with the placebo.   
  [Regimen] 
Once-weekly dosing was set as the standard administration method because the safety 
of this administration method was confirmed in the phase 1 trial (Trial 311-10-001).  
Considering that other cancer treatment vaccines were administered 6 to 12 times 
weekly28 29 30 31 or once every two weeks,32 33 the IMP will be administered once a 
week until the 8th administration and will be administered once every two weeks 
from the 9th administration onward.  The IMP will be administered subcutaneously in 
the same manner as in the phase 1 trial. 
[Treatment period] 
See Section 3.2, Rationale for Trial Design  
 
6.2 
Prior and Concomitant Treatment 
If a drug (except for components of water for injection such as a saline or dextrose in 
water) other than the IMP has been used during the period from 4 weeks before IMP 
administration to the completion examination or withdrawal examination, the name of the 
drug, purpose of use, daily dose, route of administration, and dates of start and 
completion of administration, whether or not prior treatment has been ongoing from 4 
weeks before commencement of IMP administration, and whether or not concomitant 
treatment is continued after the completion examination visit or withdrawal examination 
visit will be recorded in the case report form (CRF).  For non-drug treatments, the name 
of the treatment, its purpose, the dates of start and completion of the treatment, whether 
or not prior treatment has been ongoing from 4 weeks before commencement of IMP 
administration, and whether or not concomitant treatment is continued after the 
completion examination visit or withdrawal examination visit will be recorded in the 
CRF. 
6.2.1 
Prohibited Concomitant Drugs and Therapies 
Only the IMP will be used for treating the primary disease (AML), and concomitant use 
of the drugs (including Chinese herbal medicine) and therapies listed below is prohibited 
from the time of informed consent to the end of the post-treatment examination.  If a 
subject requires treatment with a prohibited concomitant drug or therapy, the subject 


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should be withdrawn from the trial according to Section 9.2, Criteria and Procedures for 
Withdrawal of Individual Subjects.   
 Other anti-cancer drugs, hormone therapy, antibody therapy, radiation therapy, 
thermal therapy or other anti-cancer therapies 
 Systemic administration of corticosteroids (equivalent to > 10 mg/day of 
prednisolone for 2 weeks or longer) and systemic administration of drugs 
potentially affecting the immune system, including immunosuppressants and 
immunostimulants 
 G-CSF and GM-CSF 
 Topical application of corticosteroids at the IMP injection sites 
 Investigational drugs and individually imported drugs 
 
[Rationale for establishing the prohibited concomitant drugs and therapies] 
The above-defined prohibited concomitant drugs and therapies were set because there 
is a possibility of these drugs or therapies affecting safety and efficacy assessments. 
 
6.3 
Method of Minimizing or Avoiding Bias 
The treatment allocation code will be double-blinded during the treatment period, 
meaning neither the investigator nor the subject will know whether the treatment 
administered is OCV-501 or placebo.  The sponsor’s trial personnel, such as those 
involved in monitoring, data management, and data analysis, including personnel 
belonging to contract research organizations (CROs), will not have access to the 
treatment allocation code during the conduct of the trial.  Only the subject randomization 
center will have access to the treatment allocation code for this trial, and only if it is 
needed in an emergency.   
OCV-501 vials and placebo vials will be indistinguishable in appearance and shape.   
Blinding is critical to the integrity of this trial.  However, in the event that a subject 
experiences a medical emergency in which knowledge of the IMP is critical to the 
subject’s management, the blind may be broken by the investigator.  The need to break 
the blind must first be discussed with the sponsor and the best method to do this will be 
determined.  The treatment allocation code should be kept confidential and revealed only 
to those individuals that must be informed for medical management of the subject.  See 
Section 8.2.4 for procedural details. 


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For measurement of the OCV-501-specific IFN-γ production, WT1-killer peptide specific 
IFN-γ production, anti-OCV-501 antibody level, and anti-WT1 antibody level, the results 
will not be revealed until unblinding at conclusion of the trial.  If a medical emergency 
occurs in a subject and knowledge of his or her IMP randomization code is considered 
important for treatment, the emergency code will be broken according to Section 8.2.4, 
Emergency Code Breaking (Procedure for Unblinding During the Trial Period). 
The randomization will be stratified by two stratification factors: country/region (Japan, 
Republic of Korea, Taiwan), and age at the time of providing informed consent (60 to 64 
years, 65 to 70 years, and ≥ 71 years) to minimize imbalances between the treatment arms. 
7 
Trial Procedures 
7.1 
Schedule and Procedures  
The schedule of observations, examinations, and evaluations is shown in Table 7.1-1.  
The investigator or subinvestigator will perform observations, examinations, and 
evaluations in accordance with this schedule.  Items that trial associates are capable of 
performing, such as the subject background survey, may be performed by trial associates 
under the supervision of the investigator or subinvestigator.   
 


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Table 7.1-1 
Trial Schedule 
Procedure 
  
Screening 
period 
Treatment period 
Post-treatment observation 
period *1 
W1 to W8 (once-weekly IMP administration) 
W9 to W104 (every two weeks IMP administration) 
Completion 
Withdrawal 
(Week) 
W1 
W2 
W3 
W4 
W5 
W6 
W7 
W8 
W9 
W11 
W13 
W15 
After Week 17 up to Week 102 
W103 W104 
(Day) 
D1 
D8 
D15 
D22 
D29 
D36 
D43 
D50 
D57 
D71 
D85 
D99 
D715 D722 
D729 
Within 7 days 
from 
withdrawal 
judgment 
(Allowance) 
  
1 
5 - 11 
12 - 
18 
19 - 
25 
26 - 
32 
33 - 
39 
40 - 
46 
47 - 
53 
54 - 
60 
66 - 
76 
80 - 
90 
94 - 
104 
Same as W11 to W15 
（up to Week 102） 
710 - 
720 
- 
11 - 17 days 
after W 103 
Written informed consent 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Information 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virus test a) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest x ray 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
hCG pregnancy test b) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body height 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient enrollment for this trial 
 
○ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for HLA genotyping 
 
○ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP administration c) 
 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ (every 2 weeks) 
↓ 
 
 
 
(1) 
(2) 
(3) 
(4) 
(5) 
(6) 
(7) 
(8) 
(9) 
(10) 
(11) 
(12) 
(13-55) 
(56) 
 
 
 
Concomitant drug survey 
□ 
Adverse event observation 
□ 
Medical interview by (sub)investigator 
□ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ (every 2 weeks) 
○ 
 
□ 
□ 
Body weight 
□ 
▲ 
 
 
 
□ 
 
 
 
□ 
 
□ 
 
□ (every 4 weeks) 
 
 
□ 
□ 
Vital signs d) 
□ 
▲ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
Hematology  test e) f) 
□ 
▲ 
 
○ 
 
○ 
 
○ 
 
○ 
○ 
○ 
○ 
○ (every 2 weeks) 
○ 
 
□ 
□ 
Peripheral blood smear preparation 
□ 
▲ 
 
□ 
 
□ 
 
□ 
 
□ 
□ 
□ 
□ 
□ (every 2 weeks) 
□ 
 
□ 
□ 
Blood biochemistry test g) 
□ 
▲ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
12-Lead electrocardiogram 
□ 
 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
 
 
□ 
□ 
QOL(EORTC QLQ-C30) 
 
○ 
 
 
 
□ 
 
 
 
□ 
 
□ 
 
□ (every 4 weeks) 
 
 
□ 
□ 
Performance status（ECOG PS） 
□ 
▲ 
 
 
 
□ 
 
 
 
□ 
 
□ 
 
□ (every 4 weeks) 
 
 
□ 
□ 
Bone marrow aspiration f) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
□ 
 
Bone marrow smear preparation g) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
□ 
 
Urinalysis h) 
□ 
▲ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
Expressed level of WT1 mRNA 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
IFN-γ production (OCV-501-specific, 
WT1-killer peptide specific) 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (at Weeks 25, 37, 49, 61, 73, 
85, 97) 
 
 
□ 
□ 
Anti-OCV-501 antibody 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
Anti-WT1 antibody 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
 
 
□ 
□ 
IImmunoglobulin 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
 
 
□ 
□ 


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●: Obtained before screening examinations. 
○: Mandatory (to be performed/collected before IMP administration). 
▲: Data from a screening examination can be used if they were obtained within 7 days before the IMP administration (to be performed before IMP administration except 
peripheral blood smear preparation). 
□: Mandatory  
 
a HIV antibody, HBV-DNA, HCV antibody. 
b To be performed only for female subjects who are capable of becoming pregnant (Urine test). 
c Once-weekly up to the 8th administration, once every two weeks from the 9th administration onward.  The subject’s general conditions, including injection site reaction, 
must be observed at the trial site for one hour after IMP administration. 
d Blood pressure, pulse, body temperature  
e Hb, Hct, RBC, WBC, WBC differential (visual count), PLT.  
f If leukemic blast cells appear in peripheral blood or if there is a reduction in blood cell components, perform bone marrow aspiration by post-treatment observation period, 
and prepare smear. 
g AST, ALT, ALP, LDH, γ-GTP, TP, ALB, T-Bil, BUN,UA, Cr  
h pH and specific gravity, bilirubin, glucose, ketone bodies, white blood cells, occult blood, protein, urobilinogen 
 
*1 Even if treatment is discontinued before completion of the 2-year treatment period, patients will still undergo the post-treatment examination. 
(If an AE has not resolved by the end of the post-treatment observation period, the investigator or subinvestigator will explain to the subject the need for follow-up 
investigation and will request the subject’s cooperation.  The investigator or subinvestigator will conduct a follow-up investigation within 4 weeks after the post-treatment 
observation period.)


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7.1.1 
Acquisition of Informed Consent  
The investigator or subinvestigator will obtain written consent directly from subjects prior 
to the screening examination.  After giving informed consent, each subject will be 
registered in either the IVRS or the IWRS and assigned a subject number, which will be 
recorded.  The investigator or subinvestigator will record the subject number (three-digit 
trial site number + four-digit sequential serial number) and the date of written informed 
consent on the medical records and CRF.   
7.1.2 
Screening Examination 
7.1.2.1 
Screening Examination 
After acquisition of informed consent, the following screening examination will be 
performed and subjects who meet the inclusion criteria and do not fall under any of the 
exclusion criteria will be selected.  The results of tests/assessments and the date of 
measurement/examination or the date of blood/urine collection will be recorded in the 
medical records and CRF. 
The following items will be performed at a feasible time. 
 Virus test (HIV antibody, HBV-DNA, HCV antibody) 
Virus test will be performed at the central laboratory. 
 Chest x-ray 
The chest x-ray will be performed according to the institutional standard method.  The 
results will be recorded in the medical records and CRF. 
 hCG pregnancy test (urine test) 
The pregnancy test will be performed for female subjects at the trial site.  A 
pregnancy test will not be required for subjects who have undergone bilateral 
oophorectomy or hysterectomy, or have not experienced menses for at least 12 
consecutive months for whatever other medical reasons. 
 Body weight / body height 
The measurements will be performed according to the institutional standard method.  
The results will be recorded in the medical records and CRF. 
 Survey of concomitant drugs and therapies 
 Survey of AEs 
 Medical interview by investigator or subinvestigator  
 Vital signs (blood pressure, pulse, and body temperature) 
 Hematology test (Hb, Hct, RBC, WBC, WBC differential, PLT)  
 Peripheral blood smear preparation 
 Bone marrow aspiration and bone marrow smear preparation 
Bone marrow aspiration will be performed.  The date of bone marrow aspiration and 


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result will be recorded in the medical records and CRF. 
The measurement parameters will include the following items: 
The percentage of myeoblasts/leukemia cells, lymphoblasts, erythroblast, monoblast, 
promyelocytes, myelocytes, metamyelocytes, neutrophils [Stab cell, segmented cells], 
basophiles, eosinophils,  monocytes, lymphocytes, and atypical lymphocytes. 
 Blood biochemistry tests (AST, ALT, ALP, LDH, γ-GTP, TP, ALB, T-Bil, BUN, UA 
and Cr) 
 Urinalysis (pH and specific gravity, bilirubin, glucose, ketone bodies, white blood 
cells, occult blood, protein, urobilinogen) 
 12-Lead electrocardiography (ECG) 
 Performance status (ECOG PS)  
 
7.1.2.2 
Subject Information 
At the time of obtaining informed consent or at the screening examination, the following 
subject information will be recorded in the medical records (if necessary) and the CRF. 
 Date of informed consent acquisition 
 Subject number 
 Subject’s background information:   
 Sex 
 Date of birth (year, month, day),  
 Country where the trial was conducted 
 Race 
 Information of AML and other malignancies:   
 Diagnosis of AML (WHO classification) and date of diagnosis 
 Caryotype or cytogenetic abnormalities of AML at the diagnosis 
 Existence of extranodullary disease 
 Percentage of leukemic blast (bone marrow blast) at the diagnosis  
 Regimen of induction therapy (name of drug, dose) and date of start. 
 Number of courses until CR is achieved 
 Date of CR by induction therapy 
 Regimen of consolidation therapy (name of drug, dose) and date of start. 
 Number of courses of consolidation therapy 
 Last date of administration of consolidation therapy 
 Maximum WT1 mRNA level and date of sample collection at AML diagnosis or 
at the time of induction therapy or consolidation therapy (if possible). 
 Diagnosis of malignant tumor other than AML and date of diagnosis and date of 
cure 


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 Treatment of malignant tumor other than AML 
 Medical history and concomitant disease:  
 Medically significant medical history and date of diagnosis 
 Diagnosis of concomitant disease at the time of obtaining informed consent, and 
date of diagnosis 
 
7.1.2.3 
Allocation of Investigational Medicinal Products to Subjects at 
Enrollment (Before Week 1 IMP Administration) 
From the results of the screening examination, the investigator or subinvestigator will 
verify that the subject meets the inclusion criteria and does not fall under any of the 
exclusion criteria, and each subject will be registered in either the IVRS or the IWRS and 
assigned a treatment allocation code.  Date of the enrollment will be recorded in the 
medical records and CRF. 
7.1.3 
Observations, Examinations, and Evaluations During the 
Observation Period 
7.1.3.1 
Observations, Examinations, and Evaluations From Week 1 to 
Week 8 
7.1.3.1.1 
Week 1 (1st Administration [Day 1]) 
The following observations, examinations, evaluations, and IMP administration will be 
performed.  The date and results of observations, examinations, and evaluations, and the 
date of blood samplings will be recorded in the medical records and CRF. 
1) A medical interview by investigator or subinvestigator will be performed before IMP 
administration. 
2) Blood sampling for HLA genotyping (HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-
DRB5, HLA-DPB1, HLA-DQB1, and HLA-A) will be performed. 
3) Adverse event observation and a concomitant drug survey will be performed. 
4) Subjects will receive the IMP (3 mg of OCV-501 [0.4 mL] or placebo [0.4 mL]) 
according to the IMP pack number (unique ID No.) provided through the IVRS or the 
IWRS at each scheduled visit.  The IMP pack number (unique ID No.) will be issued 
according to the treatment allocation code.  The IMP will be subcutaneously 
administered at the axilla or inguinal region.  
(The subject’s general conditions, including injection site reaction, must be observed 
at the trial site for one hour after IMP administration.) 
5) Blood sampling for measurement of WT1 mRNA expression level will be performed 
before IMP administration.  
6) QOL (EORTC QLQ-C30) self-assessment will be performed by subjects.  


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7) Blood sampling for measurement of OCV-501-specific IFN-γ production, WT1-killer 
peptide specific IFN-γ production, anti OCV-501 antibody level, anti-WT1 antibody, 
and immunoglobulin will be performed before IMP administration will be performed. 
 
If the following examinations were conducted within 7 days before IMP administration, 
the data can be used as the Day 1 examination data. 
8) Body weight measurement will be performed before IMP administration. 
9) Measurement of vital signs will be measured before IMP administration (blood 
pressure, pulse, and body temperature).  
10) Blood sampling for a hematology test will be performed before IMP administration. 
11) Peripheral blood smear preparation will be performed. 
12) Blood sampling for a blood biochemistry test will be performed before IMP 
administration. 
13) Performance status (ECOG PS) will be measured. 
14) A urine sample for urinalysis will be collected before IMP administration. 
 
7.1.3.1.2 
Weeks 2, Week 4, Week 6, and Week 8 
The margin of acceptability is ± 3 days.  The following observations, examinations, 
evaluations, and IMP administration will be performed.  The date and results of 
observations, examinations, and evaluations, and the date of blood samplings will be 
recorded in the medical records and CRF. 
1) The investigator or subinvestigator will perform a medical interview before IMP 
administration. 
2) Subjects will receive the IMP (3 mg of OCV-501 [0.4 mL] or placebo [0.4 mL]) 
according to the IMP pack number (unique ID No.) provided through the IVRS or the 
IWRS at each scheduled visit.  The IMP pack number (unique ID No.) will be issued 
according to the treatment allocation code.  The IMP will be subcutaneously 
administered at the axilla or inguinal region. 
(The subject’s general conditions, including injection site reaction, must be observed 
at the trial site for one hour after IMP administration.) 
3) Adverse event observation and a concomitant drug survey will be performed. 
 
7.1.3.1.3 
Week 3 and Week 7 
The margin of acceptability is  3 days.  The following observations, examinations, 
evaluations, and IMP administration will be performed.  The date and results of 
observations, examinations, and evaluations, and the date of blood samplings will be 
recorded in the medical records and CRF. 


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1) The investigator or subinvestigator will perform a medical interview before IMP 
administration. 
2) Samples will be collected for a hematology test before IMP administration. 
3) Peripheral blood smear preparation*. 
4) Subjects will receive the IMP (3 mg of OCV-501 [0.4 mL] or placebo [0.4 mL]) 
according to the IMP pack number (unique ID No.) provided through the IVRS or the 
IWRS at each scheduled visit.  The IMP pack number (unique ID No.) will be issued 
according to the treatment allocation code.  The IMP will be subcutaneously 
administered at the axilla or inguinal region. 
(The subject’s general conditions, including injection site reaction, must be observed 
at the trial site for one hour after IMP administration.) 
5) Adverse event observation and a concomitant drug survey will be performed. 
*: If leukemic blast cells appear in peripheral blood or if there is a clinically significant 
reduction in blood cell components, the investigator or subinvestigator will perform bone 
marrow aspiration and prepare bone marrow smears. 
 
7.1.3.1.4 
Week 5 
The margin of acceptability is ± 3 days.  The following observations, examinations, 
evaluations, and IMP administration will be performed.  The date and results of 
observations, examinations, and evaluations, and the date of blood samplings will be 
recorded in the medical records and CRF. 
1) The investigator or subinvestigator will perform a medical interview before IMP 
administration. 
2) Samples for a hematology test will be collected before IMP administration. 
3) Peripheral blood smear preparation* will be performed.  
4) Samples for a blood biochemistry test will be collected before IMP administration. 
5) A urine sample for urinalysis will be collected before IMP administration. 
6) Samples for measurement of WT1 mRNA expression level will be collected before 
IMP administration. 
7) Samples for measurement of OCV-501-specific IFN-γ production, WT1-killer peptide 
specific IFN-γ production, anti-OCV-501 antibody level, anti-WT1 antibody level, 
and immunoglobulin will be collected before IMP administration. 
8) Subjects will receive the IMP (3mg of OCV-501 [0.4 mL] or placebo) according to 
the IMP pack number (unique ID No.) provided through the IVRS or the IWRS at 
each scheduled visit.  The IMP pack number (unique ID No.) will be issued according 
to the treatment allocation code.  The IMP will be subcutaneously administered at the 
axilla or inguinal region. 
(The subject’s general conditions, including injection site reaction, must be observed 
at the trial site for one hour after IMP administration.) 


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9) QOL (EORTC QLQ-C30) self-assessment by subjects will be performed. 
10) Performance status (ECOG PS) will be measured. 
11) Vital signs will be measured before IMP administration. 
12) 12-Lead ECG will be performed before IMP administration. 
13) Body weight will be measured. 
14) Adverse event observation and a concomitant drug survey will be performed. 
*: If leukemic blast cells appear in peripheral blood or if there is a clinically significant 
reduction in blood cell components, the investigator or subinvestigator will perform bone 
marrow aspiration and prepare bone marrow smears. 
 
7.1.3.2 
Observations, Examinations, and Evaluations From Week 9 to 
Week 104 
7.1.3.2.1 
Week 9 
The margin of acceptability is ± 3 days.  The following observations, examinations, 
evaluations, and IMP administration will be performed.  The date and results of 
observations, examinations, and evaluations, and the date of blood samplings will be 
recorded in the medical records and CRF.  
1) The investigator or subinvestigator will perform a medical interview before IMP 
administration. 
2) Samples for a hematology test will be collected before IMP administration. 
3) Peripheral blood smear preparation* will be performed. 
4) Samples for a blood biochemistry test will be collected before IMP administration. 
5) A urine sample for urinalysis will be collected before IMP administration. 
6) Samples for measurement of WT1 mRNA expression level will be collected before 
IMP administration. 
7) Samples for measurement of OCV-501-specific IFN-γ production, WT1-killer peptide 
specific IFN-γ production, anti-OCV-501 antibody level, anti-WT1 antibody level, 
and immunoglobulin will be collected before IMP administration. 
8) Subjects will receive the IMP (3 mg of OCV-501 [0.4 mL] or placebo) according to 
the IMP pack number (unique ID No.) provided through the IVRS or the IWRS at 
each scheduled visit.  The IMP pack number (unique ID No.) will be issued according 
to the treatment allocation code.  The IMP will be subcutaneously administered at the 
axilla or inguinal region. 
(The subject’s general conditions, including injection site reaction, must be observed 
at the trial site for one hour after IMP administration.) 
9) QOL (EORTC QLQ-C30) self-assessment by subjects will be performed. 
10) Performance status (ECOG PS) will be measured. 
11) Vital signs will be measured before IMP administration. 


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12) 12-Lead ECG will be performed before IMP administration. 
13) Body weight will be measured. 
14) Adverse event observation and a concomitant drug survey will be performed. 
*: If leukemic blast cells appear in peripheral blood or if there is a clinically significant 
reduction in blood cell components, the investigator or subinvestigator will perform bone 
marrow aspiration, and prepare bone marrow smears. 
 
7.1.3.2.2 
From Week 11 to Week 104 
The margin of acceptability is ± 5 days.  The following observations, examinations, 
evaluations, and OCV-501 administration will be performed on odd numbered weeks 
(Week 11, 13, 15, 17, 19, 21, etc).  The date and results of observations, examinations, 
and evaluations, and the date of blood samplings will be recorded in the medical records 
and CRF. 
1) The investigator or subinvestigator will perform a medical interview before IMP 
administration. 
2) Samples for a hematology test will be collected before IMP administration. 
3) Peripheral blood smear preparation* will be performed. 
4) Subjects will receive IMP (3 mg of OCV-501 [0.4 mL] or placebo) according to the 
IMP pack number (unique ID No.) provided through the IVRS or the IWRS at each 
scheduled visit.  The IMP pack number (unique ID No.) will be issued according to 
the treatment allocation code.  The IMP will be subcutaneously administered at the 
axilla or inguinal region. 
(The subject’s general conditions, including injection site reaction, must be observed 
at the trial site for one hour after IMP administration.) 
5) Adverse event observation and a concomitant drug survey will be performed. 
*: If leukemic blast cells appear in peripheral blood or if there is a clinically significant 
reduction in blood cell components, the investigator or subinvestigator will perform bone 
marrow aspiration by post-treatment observation period, and prepare bone marrow smears. 
 
The following observations, examinations, and evaluations will be performed every 4 
weeks (Week 13, 17, 21, etc).  
 Samples for a blood biochemistry test will be collected before IMP 
administration. 
 A urine sample for urinalysis will be collected before IMP administration. 
 Samples for measurement of WT1 mRNA expression level will be collected 
before IMP administration. 


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 Samples for measurement of anti-OCV-501 antibody level, anti-WT1 antibody 
level, and immunoglobulin will be collected before IMP administration.  
 QOL (EORTC QLQ-C30) self-assessment by subjects and performance status 
(ECOG PS) measurement will be performed, and body weight will be 
measured. 
 Vital signs will be measured and 12-Lead ECG will be performed before the 
IMP administration. 
 
The following blood collection will be performed every 12 weeks (Week 13, 25, 37, 49, 
61, 73, 85, and 97). 
 Samples for measurement of OCV-501-specific IFN-γ production, and WT1-
killer peptide specific IFN-γ production will be collected before IMP 
administration.  
 
7.1.4 
Observations, Examinations, and Evaluations During the Post-
Treatment Observation Period 
7.1.4.1 
Observations, Examinations, and Evaluations at 11 to 17 days 
After Week 103 (Completion Examination) 
For the completion examination, the following examinations and observations will be 
performed.  The date and results of observations, examinations, and evaluations, and the 
date of blood samplings will be recorded in the medical records and CRF.   
1) The investigator or subinvestigator will perform a medical interview. 
2) Samples will be collected for a hematology test and peripheral blood smear 
preparation. 
3) Samples will be collected for a blood biochemistry test. 
4) A urine sample for urinalysis will be collected. 
5) 12-Lead ECG will be performed. 
6) Vital signs (blood pressure, pulse rate, and body temperature) will be measured. 
7) Body weight will be measured. 
8) Adverse event observation and a concomitant drug survey will be performed. 
9) QOL (EORTC QLQ-C30) self-assessment by subjects will be performed. 
10) Performance status (ECOG PS) will be measured. 
11) Samples will be collected for measurement of WT1 mRNA expression level.  
12) Samples will be collected for measurement of OCV-501-specific IFN-γ production, 
WT1-killer peptide specific IFN-γ production, anti-OCV-501 antibody level, anti-
WT1 antibody level, and immunoglobulin. 
13) Bone marrow aspiration and bone marrow smear preparation will be performed. 


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7.1.4.2 
Time of Withdrawal and Withdrawal Examination 
At the time of withdrawal, the following examinations, observations, and evaluations will 
be performed within 7 days from the day on which withdrawal was judged to be 
necessary.  If the subject refuses to undergo any examinations at the time of withdrawal, 
or if the investigator or subinvestigator judges that any examinations cannot be performed 
due to an emergency or other circumstances (eg, SAE or relapse of AML), of the 
examination items specified for the time of withdrawal, only those items that can be 
performed will be performed.  The date and results of observations, examinations, and 
evaluations, and the date of blood samplings will be recorded in the medical records and 
CRF.  
1) Adverse event observation and a concomitant drug survey will be performed. 
2) The investigator or subinvestigator will perform a medical interview. 
3) Body weight will be measured. 
4) Vital signs (blood pressure, pulse rate, and body temperature) will be measured. 
5) 12-Lead ECG will be performed. 
6) Blood sampling for a hematology test and peripheral blood smear preparation* will be 
performed. 
7) Blood sampling for a blood biochemistry test will be performed.  
8) A urine sample for urinalysis will be collected. 
9) QOL (EORTC QLQ-C30) self-assessment by subjects will be performed. 
10) Performance status (ECOG PS) will be measured. 
11) Samples will be collected for measurement of WT1 mRNA expression level. 
12) Blood sampling for measurement of OCV-501-specific IFN-γ production, WT1-killer 
peptide specific IFN-γ production, anti-OCV-501 antibody level, anti-WT1 antibody 
level, and immunoglobulin will be performed. 
*: If leukemic blast cells appear in peripheral blood or if there is a clinically significant 
reduction in blood cell components, the investigator or subinvestigator will perform bone 
marrow aspiration, and prepare bone marrow smears. 
 
7.1.5 
Follow-up Investigation   
7.1.5.1 
Adverse Events 
If an AE has not resolved by the end of the post-treatment observation period, additional 
investigations will be performed in accordance with Section 8.4, Follow-up Investigation 
of Adverse Events.  


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7.1.6 
Outcome Observation 
7.1.6.1 
Overall Survival 
All patients will be surveyed for survival by the date of cutoff. 
The cutoff date was set as the date after 728 days (2 years) from the day that the last 
subject started IMP administration.  The outcome and dates of any events or reason for 
censoring (if censored) will be recorded in the CRF. 
7.1.6.2 
Post Treatment for AML 
Post treatment (drugs or therapies) for AML after this trial will be surveyed from the last 
dose of the IMP until the cutoff date for the overall survival for all patients.  The start 
date and regimen of post treatment will be recorded in the medical records and CRF. 
If relapse is observed after the post-treatment examination period in any patients who did 
not show any relapse up to the post-observation period, the date of relapse will also be 
surveyed up to the cutoff date of OS.  The data will be recorded in the medical records 
and CRF. 
7.2 
Method of Evaluation 
7.2.1 
Efficacy Evaluation 
7.2.1.1 
Relapse of AML Based on the Response Criteria of the 
International Working Group 
Hematology tests will be performed in the screening period and every two weeks during 
the treatment period.  If leukemic blast cells appear in peripheral blood or if there is a 
clinically significant reduction in blood cell components, bone marrow aspiration will be 
performed.  The results will be assessed according to the response criteria of the 
International Working Group shown in Table 7.2.1.1-1 and the assessment will be 
recorded in the medical records and CRF.  Trial sites will prepare extra smears other than 
for evaluation in the trial site from bone marrow and peripheral blood in all scheduled 
tests performed during the trial (from screening period to post-treatment observation 
period), and prepare the MG staining* or WG staining* sample according to the 
procedures of the trial site (to protect subjects’ personal information, only subject 
numbers and the name of staining method will be written on smears).  The percentage of 
leukemic blast cells and other differential white blood cell counts in the prepared 
specimen will be measured at the trial site and the result along with the date of blood 
collection will be recorded in the medical records and the CRF. 


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* Both staining methods are acceptable, but only one method may be used for each 
subject. 
The sponsor will collect the smears prepared during the trial (from screening period to 
post-treatment observation period) and retrospective evaluation of samples will be 
conducted by the central pathological review committee.  The central pathological review 
committee will evaluate samples used at the judgment of relapse by the trial site and the 
previous sample from before relapse, and verify the judgment of relapse of the trial site. 
(If possible, the trial site will prepare a peroxidase-stained smear, a specific esterase-
stained smear, and a nonspecific esterase-stained [α-naphthyl-butyrate-esterase-stained 
and/or α-naphthyl-acetate-esterase-stained] smear from bone marrow and submit them to 
the sponsor when relapse has been judged at the trial site.) 
If a subject does not show relapse at the completion examination, or if a patient 
discontinues treatment without relapse before the end of the post-treatment observation 
period, the central pathological review committee will evaluate samples at the completion 
examination or withdrawal examination and confirm that the patient has no relapse. 
The investigator or subinvestigator will assess the DFS, and will record the outcome and 
dates of any events or reason for censoring (if censored) in the medical record and CRF. 
 
Table 7.2.1.1-1 
Assessment of Therapeutic Response by Response Criteria35 
Complete Remission 
A case that meets all of the following criteria will be designated as complete 
remission. 
1. The bone marrow contains less than 5% blast cells and no Auer rods. 
2. The patient has an absolute neutrophil count of > 1,000/μL 
3. The patient has a platelet count of ≥ 100,000/μL. 
4. The patient is independent of transfusion. 
5. There is no residual evidence of extramedullary leukemia. 
Relapse 
(morphologic relapse) 
A case will be designated as relapse if any of the following occur. 
Reappearance of leukemic blast cells in the peripheral blood or ≥ 5% blast 
cells in the bone marrow after CR  
(If chromosome analysis is conducted during the trial period, any cases that show reappearance of 
leukemia cells with chromosomal aberrations [cytogenetic relapse] or appearance of extranodullary 
disease will be handled as cases of relapse） 
 
7.2.1.2 
Quality of Life (QOL) (The European Organization for Research 
and Treatment of Cancer [EORTC] QLQ-C30) 
At the specified times, each subject will assess his/her own QOL status according to the 
criteria of the EORTC QLQ-C30.  The investigator or subinvestigator will record the date 


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and the results of assessment in the CRF.  The original survey slip filled out by each 
subject will be stored in the medical records. 
7.2.1.3 
Performance Status (The Eastern Cooperative Oncology Group 
performance status [ECOG PS]) 
The investigator or subinvestigator will assess performance status according to the criteria 
of ECOG PS and record the date and results of evaluation in the medical records and CRF.  
 
ECOG Performance Status* 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work 
2  
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours  
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
* As published in Am. J. Clin. Oncol.: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, 
T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative 
Oncology Group. Am J Clin Oncol 5:649-655, 1982 . 
 
7.2.2 
Safety Evaluation 
7.2.2.1 
Body Weight 
Body weight will be measured according to the procedure specified by the trial site, and 
the date and the results of measurement will be recorded in the medical records and CRF.  
If body weight is measured to the second decimal place, the value will be rounded to the 
first decimal place.  
7.2.2.2 
Vital Signs (Body Temperature, Blood Pressure, and Pulse 
Rate)  
Systolic and diastolic blood pressures, pulse rate, and body temperature will be measured 
at rest according to the procedures specified by the trial site, and the date of evaluation 
and the result will be recorded in the medical records and CRF.   


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7.2.2.3 
Clinical Laboratory Tests (Hematology test, Blood 
Biochemistry Test) and Urinalysis 
The central laboratory will measure the endpoints listed in Table 7.2.2.3-1.  The volume 
of blood sampling is shown in Annex 3. 
The investigator or subinvestigator will review the analysis report from the central 
laboratory, and date and sign the analysis report. 
 
Table 7.2.2.3-1 
Clinical Laboratory Tests (Central Laboratory)- Listing 
Hematology Test 
Hemoglobin (Hb) 
Hematocrit (Hct) 
Red blood cell count (RBC) 
White blood cell count (WBC) 
Platelet count (PLT) 
Blood Biochemistry Test 
Aspartate transaminase (AST) 
Alanine transaminase (ALT) 
Alkaline phosphatase (ALP) 
Lactate dehydrogenase (LDH) 
γ - glutamyltransferase (γ-GTP) 
Total protein (TP) 
Albumin (ALB) 
Total bilirubin (T-BIL) 
Blood urea nitrogen (BUN) 
Uric acid (UA) 
Creatinine (Cr) 
 
Differential leukocyte count (myeloblasts/leukemia cells, lymphoblasts, erythroblasts, 
monoblasts, promyelocytes, myelocytes, metamyelocytes, neutrophils [Stab cell, 
segmented cells], basophiles, eosinophils, monocytes, lymphocytes, and atypical 
lymphocytes) and urinalysis (pH and specific gravity, bilirubin, glucose, ketone bodies, 
white blood cells, occult blood, protein, urobilinogen) will be measured by each trial site.  
The date of sampling and the result will be recorded in the medical records and the CRF.  
For urine collection, the information on whether collection was performed in a fasting 
state or not will be recorded in the medical records and the CRF. 
7.2.2.4 
12-Lead Electrocardiography 
The investigator or subinvestigator will measure 12-lead ECG parameters according to 
the procedures of the trial site in the screening period and at least once every four weeks 
in the treatment period.  The central ECG laboratory will electronically collect 12-lead 
ECG data and determine heart rate, PR interval, QRS complex, QT interval and QTc 
interval (QTcF= QT interval/[R-R interval]1/3).  The central ECG laboratory will report 
the analysis results to the investigator or subinvestigator.  The investigator or 
subinvestigator will then review the results, and date and sign the analysis report.  The 
investigator or subinvestigator will also reconfirm the normality/abnormality judgment by 


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referring to the analysis report provided by the central ECG laboratory, and record the 
reconfirmation date in the medical records and CRF, along with the date and time of the 
ECG measurement.  Any clinically significant findings will be evaluated as AEs. 
7.2.2.5 
Medical Interview 
The investigator or subinvestigator will conduct medical interview at every scheduled 
visit and will record the results of the medical interview in the medical records and will 
evaluate any clinically significant events as AEs.  AEs will be recorded in the CRF. 
7.2.2.6 
Adverse Events 
The investigator or subinvestigator will assess the nature and severity of AEs and record 
the results in the CRF (see Section 8, Adverse Events). 
7.2.2.7 
Concomitant Drug Survey 
The investigator or subinvestigator will conduct concomitant drug survey and record the 
results in the CRF (see Section 6.2, Prior and Concomitant Treatment). 
7.2.3 
Evaluation of Exploratory Items 
The volume of blood sampling is shown in Annex 3. 
7.2.3.1 
WT1 mRNA Expression Level 
1) A blood sample will be collected using a blood-collection tube containing EDTA and 
the date will be recorded in the medical records, in CRF and on the test request form. 
2) Immediately after collection, the blood will be mixed by gently inverting the tube 
several times and will then be stored refrigerated.  After the necessary items in the test 
request form have been filled out, a request for sample collection will be made to the 
test laboratory. 
3) The central laboratory will measure the level of expression of WT1 mRNA of all 
subjects and will submit the inspection report to the trial site and to the sponsor.  The 
investigator or subinvestigator will then review the results, and date and sign the 
inspection report. 
 
7.2.3.2 
OCV-501-Specific IFN-γ Production and WT1-killer Peptide 
Specific IFN-γ Production 
1) A blood sample will be collected using a vacuum blood collection tube provided by 
the sponsor and the date and time will be recorded in the medical records, in the CRF 
and on the test request form.  (The planned sampling date and time should be 
previously notified to the central laboratory to permit the central laboratory to treat the 
sample within 24 hours after sampling.  After the necessary items in the test request 


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form have been filled out, a request for sample collection will be made to the central 
laboratory.) 
2) Immediately after collection, the blood will be mixed by gently inverting the tube 
several times and will then be left at room temperature until the central laboratory 
collects the sample.   
3) The central laboratory will measure the amount of OCV-501-specific IFN-γ and 
WT1-killer peptide specific IFN-γ production of all subjects after preparing 
peripheral-blood mononuclear cells (PBMC) and will keep the inspection report under 
lock and key until unblinding. 
4) After unblinding, the central laboratory will submit the inspection report to the 
sponsor. 
5) The residual sample will be cryopreserved at or below − 65°C until completion of the 
clinical study report for this trial and, then will be discarded. 
 
7.2.3.3 
Anti-OCV-501 Antibody and Anti-WT1 Antibody 
1) A blood sample will be collected using a blood-collection tube containing a 
procoagulant agent and the date will be recorded in the medical records and CRF and 
on the test request form. 
2) Immediately after collection, the blood will be mixed by gently inverting the tube 
several times and will then be left at room temperature for about 30 minutes.  The 
serum specimen obtained after centrifuging the tube at 1800 × G for 10 minutes at 
about 4C will be divided into sample stock tubes in duplicate.  The specimen will be 
immediately cryopreserved at or below − 65°C and after the necessary items in the 
test request form have been filled out, a request for sample collection will be made to 
the central laboratory. 
3) The central laboratory will measure anti-OCV-501 antibody level and anti-WT1 
antibody level of all subjects and will keep the inspection report under lock and key 
until unblinding. 
4) After unblinding, the central laboratory will submit the inspection report to the 
sponsor. 
5) The residual sample will be cryopreserved at or below − 65°C until completion of the 
clinical study report for this trial and then will be discarded. 
 
7.2.3.4 
Immunoglobulin 
1) A blood sample will be collected using a blood-collection tube containing a 
procoagulant agent and the date will be recorded in the medical records and CRF and 
on the test request form. 
2) Immediately after collection, the blood will be mixed by gently inverting the tube 
several times and will then be left at room temperature for about 30 minutes.  The 
serum specimen obtained after centrifuging the tube at 1800 × G for 10 minutes at 


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room temperature will be divided into sample stock tubes.  The specimen will be 
immediately refrigerated and after the necessary items in the test request form have 
been filled out, a request for sample collection will be made to the central laboratory. 
3) The central laboratory will measure an immunoglobulin of all subjects and will keep 
the inspection report under lock and key until unblinding. 
4) After unblinding, the central laboratory will submit the inspection report to the 
sponsor. 
 
7.2.4 
Evaluation of Other Items 
7.2.4.1 
HLA Genotyping 
HLA genotyping (HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPB1, 
HLA-DQB1, and HLA-A) will be performed according to the procedures of the central 
test laboratory.  The genotyping results will not be disclosed to subjects. 
1) A blood sample will be collected using a blood-collection tube containing EDTA, and 
the date will be recorded in the medical records and CRF and on the test request form. 
2) Immediately after collection, the blood will be mixed by gently inverting the tube 
several times and will then be refrigerated.  After the necessary items in the test 
request form have been filled out, a request for sample collection will be made to the 
central test laboratory.   
3) The central test laboratory will identify the genotype by the method of polymerase 
chain reaction sequence-based typing, etc. and submit the measurement report to the 
sponsor.  Any remaining samples used in the genotyping will be disposed according 
to the procedures of the central test laboratory. 
 
7.2.5 
Investigational Medicinal Product Compliance 
The investigator or subinvestigator will record in the medical records and CRF the date 
and time of IMP administration.  If the IMP is not administered at the time specified in 
the trial protocol even just once, or if IMP administration was judged to be infeasible, the 
investigator or subinvestigator will record the details in the CRF.  Drug accountability 
will be checked by vials.  
7.3 
Measures to Be Taken for Subjects Visiting or Planning to Visit 
Other Hospitals or Departments 
At the time of obtaining informed consent, the investigator or subinvestigator will 
confirm whether or not the subject is receiving treatment at another hospital or 
department.  If the subject is receiving treatment at another hospital or department, the 
investigator or subinvestigator will inform the attending physician of that hospital or 


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department about the subject’s participation in the clinical trial and the IMP being used, 
with the subject’s consent.  The investigator or subinvestigator will also obtain and record 
in the medical records and CRF information on the treatment that the subject is receiving 
at the other hospital or department (name of disease being treated and information on the 
type of treatment or measures being implemented) and judge whether or not the subject 
should continue to participate in the trial. 


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8 
Adverse Events 
8.1 
Definitions 
8.1.1 
Adverse Event 
[ICH E2A guideline: Definition] 
Any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical 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 a medicinal product, whether or not considered related to the medicinal 
product.a 
For this trial, the term “medical product” is regarded as “IMP,” and to secure the safety of 
subjects, AEs occurring from consent to the start of IMP administration are included in 
the definition of AEs in addition to the definition given by ICH. 
If an event, symptom, or sign existing at the time of acquisition of informed consent 
worsens after acquisition of informed consent, or if an AE occurring between the 
acquisition of informed consent and start of IMP administration worsens after 
administration of the IMP, the exacerbation will be treated as a new AE. 
In this trial, relapse of AML without any related comorbidity will not be handled as an 
AE.  In the case that a comorbidity with AML associated with clinical symptoms meets 
the definition of an AE, it will be reported as an AE.   
8.1.2 
Serious Adverse Event 
A serious AE is defined as an AE corresponding to one of the events listed in 1) to 6) 
below.a 
The seriousness of AEs occurring during the period from consent to the start of IMP 
administration will also be judged.  
1) An event resulting in death 
                                                 
a“Clinical Safety Data Management”, Notification No. 227 of the Examination Division, 
Pharmaceutical Affairs Bureau dated 20 Mar 1995 (ICH E2A). 


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2) A life-threatening event 
The term “life-threatening” refers to an event in which the subject was at a risk of 
death at the time of the event.  It does not refer to an event which hypothetically 
might have caused death, had it been more severe. 
3) An event requiring in-patient hospitalization or prolongation of existing 
hospitalization for treatment 
4) An event resulting in persistent or significant disability/incapacity 
5) An event causing a congenital anomaly/birth defect 
6) A major event resulting in other situations, such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization, but 
which may jeopardize the subject or may require intervention to prevent one of the 
other outcomes listed in 1) to 5) above.  Examples of such events are intensive 
treatment in an emergency room for bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization; or development of drug 
dependency or drug abuse. 
 
Explanation of hospitalization for treatment of an SAE: 
Hospitalization for treatment means that the subject must be hospitalized at a medical 
institution for treatment of an AE, typically for at least one night.  This includes 
hospitalization for treatment of the AE in which no particular medical procedures are 
carried out (rest therapy).  However, it does not include hospitalization for undergoing 
tests or treatment for an underlying disease or complication that has not worsened since 
the subject’s entry into the trial, hospitalization for social reasons or convenience not 
intended for treatment of the AE, or hospitalization for treatment or tests scheduled prior 
to participation in the trial. 
8.2 
Response to Occurrence of Adverse Events 
8.2.1 
Actions to Be Taken for Subjects 
The investigator or subinvestigator will provide adequate medical care for all clinically 
significant, trial-related AEs throughout the period of subject participation in the trial as 
well as thereafter.  If treatment for an AE is necessary, the subject will be informed of this. 
8.2.2 
Expedited Reporting of Serious Adverse Events and Events 
Specified by the Sponsor 
(1) Serious Adverse Events Requiring Expedited Reporting 
1) Any SAEs occurring during the trial period regardless of causal relationship with the 
IMP 


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2) SAEs occurring during the follow-up period (see Section 8.4, Follow-up Investigation 
of Adverse Events), if a follow-up investigation is performed, for which a causal 
relationship with the IMP cannot be ruled out, or AEs that become serious during the 
follow-up period for which a causal relationship with the IMP cannot be ruled out 
3) Among SAEs occurring after completion of the trial (after the follow-up investigation, 
if a follow-up investigation is performed) and reported by subjects to the investigator 
or subinvestigator, those for which the investigator or subinvestigator cannot rule out 
a causal relationship with the IMP 
 
(2) Procedures for Expedited Reporting 
Countries/Regions other than Japan: 
1) When an AE falling under any of the above items (1) 1) to 3) occurs, the investigator 
or subinvestigator will notify the sponsor promptly after becoming aware of the event 
(within 24 hours, in principle) by facsimile (refer to Annex 1, Emergency Contact). 
The notification to the sponsor must include at least the following information. 
Subject’s date of birth, sex, starting date of IMP, information of AE, causal 
relationship with the IMP 
2) The investigator or subinvestigator will then promptly submit a detailed report on any 
SAEs occurring after the start of IMP administration to the head of the trial site and 
the sponsor within the period specified by the applicable regional requirements after 
becoming aware of them using the report form of the trial site or sponsor.  Any 
additional information will also be promptly relayed to the sponsor (within 24 hours) 
by facsimile, and additional reporting will be performed if necessary. 
3) When the investigator or subinvestigator is requested by the sponsor, the head of the 
trial site, or the IRB to prepare additional information (autopsy report, terminal care 
report, or other required information) on a reported SAE, the investigator or 
subinvestigator will respond to the request. 
 
Japan: 
1) When an AE falling under any of the above items (1) 1) to 3) occurs, the investigator 
or subinvestigator will notify the sponsor promptly after becoming aware of the event 
(within 24 hours, in principle) by facsimile (refer to Annex 1, Emergency Contact). 
The notification to the sponsor must include at least the following information. 
Subject’s date of birth, sex, starting date of IMP, information of AE, causal 
relationship with the IMP 
2) The investigator or subinvestigator will then promptly submit a detailed report on any 
SAEs occurring after the start of IMP administration to the head of the trial site and 
the sponsor within 10 days after becoming aware of them using the report form of the 
trial site or sponsor.  Any additional information will also be promptly relayed to the 
sponsor (within 24 hours) by facsimile, and additional reporting will be performed if 
necessary. 


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3) When the investigator or subinvestigator is requested by the sponsor, the head of the 
trial site, or the IRB to prepare additional information (autopsy report, terminal care 
report, or other required information) on a reported SAE, the investigator or 
subinvestigator will respond to the request. 
 
8.2.3 
Expedited Reporting of Non-serious Adverse Events Resulting in 
Discontinuation of IMP Administration 
When a non-serious AE occurs for which the investigator or subinvestigator judges that 
IMP administration should be discontinued (but not when IMP administration is merely 
temporarily interrupted), the investigator or subinvestigator will notify the sponsor within 
3 working days in principle after their judgment by facsimile (refer to Annex 1, 
Emergency Contact). 
8.2.4 
Emergency Code Breaking (Procedure for Unblinding During the 
Trial Period)   
The investigator will not open the treatment allocation code UNLESS knowledge of the 
subject’s treatment is required for the subject’s clinical care and safety.  The investigator 
or subinvestigator will contact the sponsor by any means available, including by 
telephone, with an explanation of the need for opening the treatment allocation code 
before opening the code or within 24 hours of opening the code, and shall confer with the 
sponsor regarding the decision to break the blind if he/she can contact the sponsor before 
opening the code. 
Documentation of breaking the blind will be recorded in the subject’s medical records 
with the date and time the blind was broken and the names of the personnel involved.  
IMP administration will be discontinued, and the data obtained will be promptly fixed 
and evaluated within one week. 
8.3 
Assessment of Adverse Events 
The investigator or subinvestigator will assess AEs for the following items. 
8.3.1 
Terms for Adverse Events 
If the disease responsible for an AE can be specified, the name of the diagnosed disease 
will be recorded in the CRF and not the individual symptoms. 
8.3.2 
Date of Onset and Recovery 
(1) Date of onset: 


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The date of onset of an AE or date of confirmation of an AE will be recorded in the 
medical records and CRF.  If an event, symptom, or sign existing at the time of 
acquisition of informed consent worsens, the date of exacerbation will be recorded in the 
CRF as “date of onset of AE.”  Also, if an AE occurring between the acquisition of 
informed consent and start of IMP administration worsens after administration of the IMP, 
the exacerbation will be recorded in the CRF as a new AE with the date of exacerbation 
recorded as “date of onset of exacerbated AE.” 
(2) Date of recovery:   
The date of recovery of an AE or date of confirmation of recovery of an AE will be 
recorded in the medical records and CRF. 
8.3.3 
Severity 
Severity of AEs will be classified using the Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.0 into five categories (Grade 1 to Grade 5).  
8.3.4 
Causal Relationship With Investigational Medicinal Product 
The causal relationship between the IMP and AEs occurring after the start of IMP 
administration will be judged according to the following five categories.  The causal 
relationship with the IMP will be recorded in the CRF. 
1) Definitely related: 
There is a reasonable causal relationship between the IMP and the AE, when the event 
responds to withdrawal of the IMP (dechallenge), and recurs with rechallenge by 
administration of the IMP. 
2) Probably related: 
There is a reasonable causal relationship between the IMP and the AE.  The event 
responds to dechallenge.  Rechallenge not required. 
3) Possibly related: 
There is a reasonable causal relationship between the IMP and the AE.  Dechallenge is 
lacking or unclear. 
4) Unlikely related:  
There is a temporal relationship to IMP administration, but there is not a reasonable 
causal relationship between the IMP and the AE. 
5) Not related: 
There is no temporal or causal relationship to IMP administration. 


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The five categories described above will be considered as follows:  “definitely related”, 
“probably related”, and “possibly relate” will be taken to mean “relationship with the IMP 
cannot be ruled out” and will be reported as an “adverse drug reaction”;  “unlikely 
related” and “not related” will be taken to mean “relationship to the IMP can be ruled 
out.”  
8.3.5 
Actions to Be Taken Regarding IMP Administration 
Actions to be taken regarding IMP administration following the occurrence of an AE after 
initiation of IMP administration will be selected from among the following.  Actions to 
be taken regarding IMP administration will be recorded in the CRF. 
 No change 
 Discontinuation of IMP administration 
 Interruption of IMP administration 
 Unknown  
 Not applicable 
 
8.3.6 
Actions to Be Taken for Adverse Events 
The performance of medical treatments (medications and/or other treatments) for AEs 
and details of the treatments will be described in the medical records and CRF. 
In addition, the information in case of discontinuation, withdrawal or change of 
concomitant drugs in response to occurrence of an AE will be described in the CRF. 
8.3.7 
Outcome 
The outcome of an AE will be selected from the following six categories (one only). 
If the subject died, the date of death will be recorded in the CRF; if the subject’s 
condition was recovering/resolving, not recovered/not resolved, or unknown, the date of 
outcome confirmation will be recorded in the CRF. 
 Recovered/resolved 
 Recovering/resolving 
 Not recovered/not resolved 
 Recovered/resolved with sequelae 
 Fatal 
 Unknown (for some reason, a follow-up investigation could not be performed even 
once) 
 


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8.4 
Follow-up Investigation of Adverse Events  
The term “recovered” used below means that a subject who had an AE prior to the start of 
IMP administration returned to his or her original condition, or a subject who had an AE 
after the start of IMP administration returned to his or her condition before the start of 
IMP administration. 
1) If an AE has not resolved by the end of the post-treatment examination, the 
investigator or subinvestigator will explain to the subject the need for follow-up 
investigation and will request the subject’s cooperation.  The investigator or 
subinvestigator will conduct a follow-up investigation within 4 weeks after the end of 
the post-treatment examination and record information regarding the AE in the 
subject’s medical records.  If an AE has not resolved by the end of the end of the post-
treatment examination, the investigator or subinvestigator will record the outcome in 
the CRF as “recovering/resolving”, “not recovered/not resolved”, or as otherwise 
appropriate.  
2) If an AE has not resolved by the end of the post-treatment examination and a causal 
relationship with the IMP cannot be ruled out, follow-up investigation will be 
continued until the event resolves or becomes stable and information regarding the 
AE will be recorded in the subject’s medical records.  If a causal relationship between 
the AE and the IMP can be ruled out, no further follow-up will be made beyond the 
day of the initial follow-up investigation.  
3) If, between the end of the post-treatment examination and the day of the follow-up 
investigation, a new SAE for which a causal relationship with the IMP cannot be 
ruled out occurs, or if an AE that has not resolved by the end of the post-treatment 
examination period and for which a causal relationship with the IMP cannot be ruled 
out becomes serious, follow-up investigation will be conducted until the AE resolves 
or becomes stable and information regarding the AE will be recorded in the subject’s 
medical records.   
4) If an SAE for which a relationship with the IMP cannot be ruled out is discovered 
after the end of the post-treatment examination, or after the day of the initial follow-
up investigation (if performed), follow-up investigation will be conducted until the 
AE resolves or becomes stable or until follow-up of the subject becomes impossible 
and information regarding the AE will be recorded in the subject’s medical records. 
5) If post treatment of AML is started after the end of the post-treatment observation 
period and the investigator or subinvestigator considers it difficult to confirm the 
outcome because of the effect of the post treatment, AEs will not be followed up even 
if the AE has not been resolved by the end of the post-treatment examination. 
 


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8.5 
Pregnancy  
If women of childbearing potential or male subjects whose partners are capable of 
becoming pregnant participate in the trial, the investigator or subinvestigator will attend 
to the following. 
 Information on reproductive and developmental toxicity of the IMP 
 Information regarding pregnancy in the ICF 
 Explanation of contraceptive methods  
 Reporting and follow-up of cases of pregnancy  
 
8.5.1 
Guidance to Subjects Including Contraceptive Methods 
1) Before the start of the trial, the investigator or subinvestigator will explain to the 
subjects the importance of using contraception and the risks associated with 
pregnancy of a female subject or partner of a male subject and, after subjects have 
read the written information for subjects and understood it, the investigator or 
subinvestigator will have subjects sign the ICF. 
2) If women of childbearing potential or male subjects whose partners are capable of 
becoming pregnant wish to participate in the trial, the investigator or subinvestigator 
will instruct them to practice contraception during the period specified in the trial 
protocol. 
3) Contraceptive methods include condoms, pills, pessaries, IUD, implantable 
contraceptive devices, spermicide, vasectomy, and tubal ligation.  However, if a 
female subject or male subject’s partner is without question unable to become 
pregnant (ie, has undergone bilateral ovariectomy or hysterectomy or has not 
experienced menses for at least 12 consecutive months for whatever other medical 
reasons, or the male subject/partner has undergone bilateral orchidectomy), or if the 
subject and his/her partner remain abstinent, use of contraception is unnecessary.  
4) The investigator or subinvestigator will instruct the subjects that if the contraceptive 
measures fail and evidence of pregnancy of the female subject or male subject’s 
partner such as delay in menstruation is observed, this should be promptly reported to 
the investigator or subinvestigator.  
 
8.5.2 
Actions to Be Taken by the Investigator or Subinvestigator When 
Pregnancy Is Suspected 
If the investigator or subinvestigator or a subject suspects that the subject has become 
pregnant before initiation of IMP administration, initiation of IMP administration will be 
withheld and a pregnancy test will be performed.  If the test result is positive, the trial 
subject will be withdrawn without receiving IMP administration.  If a pregnancy is 


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suspected after initiation of IMP administration, IMP administration will be discontinued 
(refer to Section 9.2, Criteria and Procedures for Withdrawal of Individual Subjects). 
The timing of reporting to the sponsor will be same as for the reporting of SAEs to the 
sponsor. 
8.5.3 
Actions to Be Taken by the Investigator or Subinvestigator When 
a Subject Is Discovered to Be Pregnant 
When a female subject is found to be pregnant, the investigator or subinvestigator will 
withdraw the subject from the trial and perform follow-up investigation until delivery or 
end of pregnancy, and report this in writing to the sponsor. 
After discontinuation of IMP administration, the investigator or subinvestigator will 
perform the withdrawal examinations and follow-up observation stipulated in the 
protocol, in so far as they do not affect the pregnancy. 
8.5.4 
Expedited Reporting of Pregnancy 
When a female subject or a partner of a male subject is found to be pregnant during the 
trial, the investigator or subinvestigator will promptly report this to the sponsor orally or 
by telephone or e-mail (refer to Annex 1, Emergency Contact).  The investigator or 
subinvestigator will then provide any additional information requested by the sponsor. 
The notification to the sponsor must include at least the following information:  
Subject’s date of birth, sex, starting date of IMP, the date and result of the pregnancy test. 
8.5.5 
Follow-up Investigation of Pregnancy 
If a female subject becomes pregnant, the investigator or subinvestigator will perform 
follow-up investigation of the pregnancy up to delivery or the end of pregnancy and 
report the results of follow-up in writing to the sponsor.  When a subject or subject’s 
partner has delivered, it is best that the neonate be observed for at least six months after 
delivery. 


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9 
Withdrawal of Individual Subjects From the Trial 
Any subject may discontinue participation in the trial at any time without medical 
disadvantage. The investigator or subinvestigator may withdraw a subject from the trial at 
any time if it is considered necessary for medical treatment of that subject.   
9.1 
Screen Failure 
If a subject is a screen failure, the following information should be recorded in the 
medical records and CRF: 
date of investigation (the start date of the screening examination), date of informed 
consent acquisition, date of birth, sex, country where the trial was conducted, race, and 
reason for screen failure. 
9.2 
Criteria and Procedures for Withdrawal of Individual Subjects 
In any of the events listed below, the investigator or subinvestigator will discontinue IMP 
administration, perform the tests to be performed at withdrawal stipulated in Section 7.1, 
Schedule and Procedures of the Trial, and promptly inform the sponsor of the withdrawal 
(Annex 1, Emergency Contact).  The investigator or subinvestigator will record the date 
and reason for withdrawal in the CRF. 
If withdrawal is necessitated by problems with safety, such as the occurrence of an AE or 
aggravation of the underlying disease, the investigator or subinvestigator will promptly 
take appropriate measures and perform follow-up if necessary (refer to Section 8.4, 
Follow-up Investigation of Adverse Events). 
1) If the patient wishes to withdraw from the trial 
2) If the investigator or subinvestigator judges that it is difficult to continue IMP 
administration due to occurrence of an AE 
3) If relapse of the primary disease (AML) is observed 
4) If a prohibited concomitant drug or therapy is used 
5) If it is later found that the patient did not to meet the eligibility criteria at the time of 
enrollment 
6) If the patient is found to be pregnant 
7) If it is not possible to administer the IMP within 21 days after obtaining informed 
consent 
8) If the investigator or subinvestigator judges that it is necessary to discontinue IMP 
administration for any another reason  
 


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9.3 
Follow-up Investigation of Subjects Who Do not Visit the Trial Site 
When a subject stops visiting the trial site for unknown reasons, the investigator or 
subinvestigator will promptly contact the subject or subject’s family by phone or other 
means to check for AEs and to ask the subject to visit. 
1) When the subject has visited 
A withdrawal examination will be performed (see Section 7.1.4.2 Time of Withdrawal). 
2) When the subject has not visited 
The following items will be recorded in the medical records and CRF. 
1. The date of investigation 
2. The method of investigation  
3. Whether or not the subject was contacted 
4. The reason why the subject does not (or cannot) visit the trial site 
5. Occurrence or non-occurrence of AEs.  If an AE has occurred:  name of the event, 
date of onset and date of recovery, severity, relationship to the IMP, measures 
taken regarding IMP administration, treatment of AE, outcome 
6. If follow-up investigation is impossible:  the reason why 
 


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10 
Collection of Case Report Form Data and Specification of 
Source Data 
10.1 
Collection of Case Report Form Data 
1) Electronic Data Capture (EDC) will be used in the trial. 
2) Subject data will be entered directly into the database from the trial site via a Web 
browser.  These data collected by EDC will constitute the CRF.  The results obtained 
from the clinical laboratory test performed by the central laboratory will be transferred 
from the central laboratory directly to the sites, except for the results of 
immunological monitoring of exploratory endpoints, HLA genotyping, and central 
pathological review, which are to be transferred to the sponsor.   
3) Regarding quality assurance of CRFs, the guidelines specified in FDA 21CFR Part11 
will be observed. 
4) For every subject who provides consent to participate in the trial, a CRF will be 
created on an EDC data entry screen that conforms to the items of CRF data 
collection described in the trial protocol.   
5) The investigator, subinvestigator, or trial associate will create CRFs according to the 
manual provided by the sponsor.  If source documents are available and the 
objectivity of the data can be ensured, then the data may be recorded in a CRF by a 
trial associate. 
6) When entering data into CRFs from the trial site, a predetermined check will be 
automatically performed.  The investigator, subinvestigator, or a trial associate will 
make corrections as necessary. 
7) The sponsor will verify CRFs in comparison to source documents and conduct data 
reviews.  If additional query is necessary, the sponsor will issue an intra-system query 
and the investigator, subinvestigator, or a trial associate will perform data correction 
or provide a response to the sponsor’s query as necessary.    
8) A history of all revisions made after the initial data entry is saved on the server will be 
automatically recorded within the system (date and time of revision, name of person 
making revision, pre- and post-revision data, reason for revision, date and time of 
query, name of person issuing query, details of query, etc). 
9) After completion of all CRF data entry and confirmation that the content is correct 
and complete, including confirmation of the audit trail, the investigator will attach an 
electronic signature. 
10) Details concerning data collection will be specified in a separate manual prepared in 
advance.  
 
10.2 Source Documents 
1) Source documents are defined as those documents that are the source of data 
transcribed into CRFs as trial results.   
Medical records and other records (eg, nursing records, prescription records), 


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registration verification forms, subject screening list, ICFs, clinical laboratory test and 
other measurement reports, ECG charts, IMP management records, and other 
documents 
2) The investigator or the trial site will retain all trial-related documents and records 
except CRFs in such a manner that enables the sponsor or the regulatory authority to 
have direct access to the documents and records. 
3) The original ICFs will be retained according to the method specified by each trial site. 
4) After completion of the trial, the sponsor will retain the original CRFs on CD-ROM 
or some other appropriate electronic medium and the investigator or the trial site will 
retain copies. 
 
10.3 Case Report Form Items to Be Treated as Source Data 
Of the data recorded in the CRF, the following items will be treated as CRF-based source 
data. 
 
Signature of investigator and date of confirmation 
 
Content of investigator or subinvestigator comment 
 
Adverse event name, severity, seriousness, actions to be taken regarding IMP 
administration, outcome, causal relationship with IMP.  
 
Reason for withdrawal 
 
Concomitant therapy or drug , dosage, route of administration, and reason (purpose) 
 
Reason for patient death after the post-treatment examination 
 
Reason for screen failure 
 
10.4 Data to Be Collected by the Sponsor 
1) CRFs (data following acquisition of informed consent)  
2) Clinical laboratory results including immunological monitoring and standard values 
(if available) 
3) Copies of 12-lead ECG charts  
4) 12-Lead ECG analysis report 
 
 


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11 
Statistical Analysis 
More specific details of the statistical analyses are described in the statistical analysis 
plan.  The statistical analyses will be fixed prior to unblinding. 
11.1 
Statistical Analysis Sets 
11.1.1 
Safety Analysis Set (SS) 
The SS includes all subjects who received the IMP at least once and from whom data on 
at least one safety endpoint was obtained after the start of IMP administration. 
11.1.2 
Full Analysis Set (FAS) 
The FAS includes all subjects who received the IMP at least once and from whom data on 
at least one efficacy endpoint was obtained after the start of IMP administration. 
11.1.3 
Per Protocol Set (PPS) 
The PPS includes all FAS subjects except those who have major protocol deviations or 
those who have withdrawn from the trial within 8 weeks from start of IMP administration.  
However, if a subject withdrew due to any reason other than an event (relapse or death) 
within 8 weeks from start of IMP administration, the subject will still be included in the 
PPS. 
11.1.4 
Immune Response Set (IRS) 
The IRS includes all subjects who received the IMP at least once and from whom data on 
at least one immune response endpoint were obtained after the start of IMP 
administration. 
11.2 
Handling of Data 
Baseline is defined as the last available screening or pre-treatment assessment. 
If a problematic subject or data are encountered, the sponsor will decide how to handle 
the subject or data, with advice from the medical expert, as necessary. 
11.3 
Analysis Items and Method 
11.3.1 
Efficacy Analysis 
FAS will be used as the primary analysis population and PPS will be used as the 
secondary analysis population to assess the stability. 


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Regarding the judgment of relapse which will be used in the primary endpoint, the 
percentage of leukemic blast cells and other differential white blood cell counts in the 
prepared specimen will be measured at the trial site and the central pathological review 
committee will evaluate and verify the judgment of relapse by the trial site.  The final 
judgment from the central pathological review committee will be taken as the main 
evaluation criteria. 
11.3.1.1 
Primary Endpoint 
1) Definition 
 Disease-free survival (DFS) 
 Observation period: For each subject, the time from randomization to the DFS-
cutoff date.  The DFS-cutoff date was set as the completion date of each subject. 
 Definition: The time from randomization until relapse or death from any cause, 
whichever comes first by the DFS-cutoff date. 
 Event: Relapse or death from any cause by the DFS- cutoff date. 
 Censoring:  
 If an event has not been observed by the DFS-cutoff date, then the last 
confirmed non-relapse date will be used as the censoring date. 
 For subjects who have withdrawn from this trial before the completion 
date for reasons other than relapses or deaths, if non-relapse has been 
confirmed on the withdrawal date, then the withdrawal date will be 
used as the censoring date. 
2) Analysis Set 
FAS, PPS 
3) Analysis Method 
Primary method:  Kaplan-Meier curve, log-rank test 
The Kaplan-Meier method will be carried out to estimate DFS functions and plot the 
DFS curve by treatment arm. 
 The log-rank test will be used to determine whether there are differences at the 
5% significance level in DFS between the OCV-501 treatment arm and the 
placebo arm. 
 The hazard ratio (OCV-501 vs. placebo) and its 95% confidence interval will be 
calculated using the wald test. 
 The 2-year survival rate and median survival time will be calculated and 95% CI 
of survival rate will be calculated using the Greenwood formula. 


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Exploratory method:   
 Harrington-Fleming Test: applying the weight 1-S(t), where S(t) is calculated 
from Kaplan Meier survival estimate. 
 HR and its 95% CI will be calculated at every 3-month interval.  The hazard rate 
will be calculated using the person-year method by treatment arm. 
 The Cox PH (Proportional Hazards) model will be used to adjust treatment 
comparison for a set of covariates which are set to be country (each country) and 
age (60 to 64 years, 65 to 70 years, and ≥ 71 years) on the time-to-event variable.  
Also, the assumption that the hazard ratio is constant over time will be graphically 
assessed by looking at the log-minus-log survival plots with stratification of 
covariates. 
 
11.3.1.2 
Secondary Endpoints 
1) Definition: 
 Overall survival (OS) 
 Observation period: For all subjects, the time from randomization to OS-cutoff 
date.  The OS-cutoff date was set as the date after 728 days (2 years) from the day 
that the last subject started IMP administration without consideration of 
withdrawal by the OS-cutoff date. 
 Definition: The time from randomization until death from any cause by the OS-
cutoff date. 
 Event: Death from any cause by the OS-cutoff date. 
 Censoring: 
 If an event has not been observed by the OS-cutoff date, then the last 
confirmed survival date will be used as the censoring date. 
 Quality of life (QOL) 
Global health status 
Functional Scale: Physical  Role  Cognitive  Emotional  Social 
Symptom Scale: Fatigue  Pain  Nausea/vomiting 
Single Items: Dyspnea  Sleep disturbance  Appetite loss  Constipation  Diarrhea Financial impact 
 
 Performance status (PS) 
 


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2) Analysis Set 
FAS, PPS 
3) Analysis Method: 
 Overall survival (OS) 
Primary method:  Kaplan-Meier curve, log-rank test  
The Kaplan-Meier method will be carried out to estimate the OS function and plot the 
OS curve of each treatment arm. 
 The log-rank test is used to determine whether there are differences at the 5% 
significance level in OS between the OCV-501 arm and the placebo arm. 
 The hazard ratio (OCV-501 vs. placebo) and its 95% confidence interval will be 
calculated using the wald test. 
 The 2-year survival rate and median survival time will be calculated and 95% CI 
of survival rate will be calculated using the Greenwood formula. 
Exploratory method:  
 Harrington-Fleming Test: applying the weight 1-S(t), where S(t) is calculated 
from Kaplan Meier survival estimate. 
 HR and its 95% CI will be calculated at every 3-month interval. The hazard rate 
will be calculated using the person-year method by treatment arm. 
 The Cox PH (Proportional Hazards) model will be used to adjust treatment 
comparison for a set of covariates which are set to be country (each country) and 
age (60 to 64 years, 65 to 70 years, and ≥ 71 years) on the time-to-event variable.  
Also, the assumption that the hazard ratio is constant over time will be graphically 
assessed by looking at the log-minus-log survival plots with stratification of 
covariates. 
 Quality of Life (QOL) 
At each time point, the scores and changes from baseline will be summarized 
using descriptive statistics by treatment arm.  Changes from baseline at each time 
point will be plotted by trend diagram. 
At each time point, the treatment effect will be estimated using the difference of 
change between the least squares means (adjusted means) of each treatment arm. 
 Performance Status (PS) 
Frequency distributions at each time point will be calculated in the OCV-501 arm 
and the placebo arm. 
 


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11.3.2 
Safety Analysis 
1) Definition:  
AEs, clinical laboratory tests, vital signs (blood pressure, pulse rate, body temperature), 
urinalysis, body weight, and electrocardiogram.  
2) Analysis Set: 
SS 
3) Analysis Method 
The analysis will be performed by each treatment arm. 
Descriptive statistics will be calculated for continuous variables and frequency 
distributions at each time point will be calculated for categorical variables. 
The object of analysis is AE occurrence after the start of IMP administration.  AEs will 
be categorized using the terminology of the Medical Dictionary for Regulatory 
Activities (MedDRA).  AEs will be tabulated by System Organ Class (SOC) and 
Preferred Term (PT), with PT substituted for verbatim terms.  The number of subjects 
and number of incidence of the following events will be tabulated per arm.  A 
summary of SAEs will be provided by severity. 
 Adverse events 
 Adverse drug reactions 
 Serious adverse events by severity 
 Adverse events leading to withdrawal 
Severity will be graded using Common Terminology Criteria for Adverse Events 
(CTCAE) version 4.0.  
4) Safety Interim Analysis 
For the purpose of data safety monitoring, the safety interim analysis will be conducted 
regularly on all subjects to provide AE tables, SAE lists, etc, while the level of blinding 
is being maintained. 
 
11.3.3 
Exploratory Items Analysis 
1) Definition:  
OCV-501 specific IFN-γ production, WT1-killer peptide specific IFN-γ production, 
anti-OCV-501 antibody level, anti-WT1 antibody level, WT1 mRNA level and 
immunoglobulin. 


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2) Analysis Set: 
IRS 
3) Analysis Method: 
Generally, a summary will be provided in terms of the mean, geometric mean, standard 
deviation, median, minimum, maximum and number of patients, unless otherwise 
stated.  Trend diagrams will be plotted by subject. 
For WT1 mRNA item, the change from baseline at each time point will be log-
transformed and t-test will be conducted between two treatment arms.  At each time 
point, a summary of descriptive statistics will be provided and trend diagrams will be 
plotted by subject. 
 
11.3.4 
Demographic and Other Baseline Characteristics 
1) Definition: 
Age, sex, height, body weight, diagnosis of AML (WHO classification)，regimen of 
induction therapy, regimen of consolidation therapy, duration from the last dose of 
consolidation therapy to randomization, maximum WT1 mRNA level at AML 
diagnosis or at the time of induction therapy or consolidation therapy, and country 
where the trial was conducted. 
2) Analysis Set: 
FAS, PPS, SS 
3) Analysis Method: 
Frequency distribution or descriptive statistics for each variable will be calculated 
according to the nature of the data (continuous or discrete). 
 
11.3.5 
Extent of Exposure 
1) Definition: 
Duration of exposure to treatment (days), full dose, total number of doses 
2) Analysis Set: 
SS 
3) Analysis Method: 
A summary of the duration of exposure to treatment and total dose will be provided. 
The descriptive statistics will be calculated by treatment arm.  


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Duration of exposure to treatment will be calculated in days as follows: 
IMP administration end date- IMP administration start date+1 
 
11.3.6 
Significance Level and Confidence Interval 
Two-sided statistical tests will be conducted at the 5% significance level and 95% 
confidence interval will be provided. 
11.3.7 
Subgroup Analysis 
1) Definition: 
The primary endpoint DFS and secondary endpoint OS will be examined for the 
following subgroups. 
Factor 
Categories 
Country/ region 
Japan, Republic of Korea, and Taiwan 
Age 
60 to 64 years, 65 to 70 years, ≥ 71 years 
 
2) Analysis Set: 
FAS 
3) Analysis Method: 
For each subgroup, summaries and statistical analysis will be conducted by treatment 
arm as follows. 
 The Kaplan-Meier method will be carried out to estimate the survivor function 
and plot the survival curve by treatment arm. 
 The hazard ratio (OCV-501 vs. placebo) and its 95% confidence interval will 
be calculated using the wald test 
 The 2-year survival rate and median survival time will be calculated and 95% 
CI of survival rate will be calculated using the Greenwood formula. 
 
11.4 
Procedures for Reporting Deviations From the Original Statistical 
Analysis Plan 
If there is any need for a change in the statistical analysis plan, the timing, details and 
reasons of the change will be included in the clinical trial report. 


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11.5 
Rationale for Target Number of Patients 
The number of AML patients is not very high, and is estimated to be approximately 7000 
in Japan36.  From the fact that in the previous clinical trial (JALSG GML200) in elderly 
AML patients, it has been forecast that the possible enrollment in Japan is to be at most 
70 in one year.  Also, from the preliminary trial feasibility survey, it is known that around 
50 subjects could be recruited in one year in Republic of Korea and Taiwan.  Through a 
global trial in Japan, Republic of Korea and Taiwan, it is considered possible to enroll 
120 subjects in one year to assess the efficacy of OCV-501.   
Within the limitation of the past experiences with regard to IMP administration, the target 
sample size will be considered with reference to following publications25,26,27,37  With 
reference to disease-free survival which has been reported from trials in AML subjects 60 
years or older who have received the consolidation therapy followed by the maintenance 
therapy, the 2-year DFS rate of placebo arm has been estimated to be around 20%.25,26,27 
On the other hand, considering the so-called graft-versus-leukemia (GVL) effect 
associated with a lower relapse risk after the allogeneic hematopoietic stem cell 
transplantation, OCV-501 is basically expected to have the same benefits.  With reference 
to the findings of Kurosawa et al,37 which have reported a 30% higher 2 or 3-year DFS in 
elderly AML subjects who have received the allogeneic hematopoietic stem cell 
transplantation compared with those without transplantation, OCV-501 is expected to 
have a 15% - 20% higher 2-year DFS.   Under the assumption of exponential distribution 
of DFS time, the hazard ratio (placebo vs. OCV-501) has been set to 0.57 - 0.65, and with 
a two-sided log-rank test at the 5% significance level, 60 or more subjects in each 
treatment group can achieve a power of 53 to 75% or more to detect the difference 
between placebo and OCV-501 groups.  
 


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Quality Control and Quality Assurance for the Trial 
To ensure the quality of the trial, trial sites, contract research organizations, laboratories 
performing clinical tests, and the sponsor will perform quality control for the trial 
according to their respective Standard Operating Procedures. 
The audit division of the sponsor company will carry out audits within the company and, 
as necessary, at the trial site and contract research organizations or organizations 
entrusted to perform related activities, and check whether quality control of the trial is 
appropriately performed according to the Standard Operating Procedures. 
 


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13 
General Items of Caution Pertaining to the Trial 
13.1 
Ethics and GCP Compliance 
This trial must be conducted in compliance with the ethical principles outlined in the 
Declaration of Helsinki, the ICH-GCP Guideline,b all applicable regional regulatory 
requirements (eg, Pharmaceutical Affairs Law, Standards for the Conduct of Clinical 
Studies [Ordinance No. 28, GCP dated 27 Mar 1997] and related notifications in Japan), 
and the protocol.   
13.2 
Institutional Review Board 
Each trial site will seek approval from an IRB/IEC according to regional regulations.  The 
IRB/IEC will investigate the ethical, scientific, and medical appropriateness of the trial.  
Further, in preparing and handling eCRFs, the investigator, subinvestigator, and their staff 
must take measures to ensure adequate care in protecting subject privacy.   
13.3 
Subject Consent 
13.3.1 
Procedures for Obtaining Consent 
1) Prior to the start of the screening examination, the investigator or subinvestigator will 
fully explain the matters listed in Section 13.3.2 to each subject who will be included 
in the trial, using the ICF, and give the ICF to the subject.  The subject will be 
provided sufficient time to make a decision regarding participation.  After confirming 
that the subject has properly understood the explanation, the investigator or 
subinvestigator will obtain written voluntary consent for participation in the trial from 
the subject. 
2) The investigator or subinvestigator who has provided the explanation and the subject 
will each put their printed name and personal seal or signature on the ICF, and write 
the date on which they sign or stamp the form.  If a trial associate has provided a 
supplemental explanation of the trial, he/she will also put his/her printed name and 
personal seal or signature on the form and write the date on which he/she signs or 
stamps the form. 
3) The original of the ICF that was signed or stamped and dated will be retained by the 
investigator or subinvestigator according to the regulations of the trial site.  A copy of 
the original ICF will be given to the subject. 
4) After obtaining informed consent from a subject, the investigator or subinvestigator 
will write the date of informed consent acquisition and subject number in the 
documents for enrolled subjects (list of screened subjects and list of enrolled subjects). 
                                                 
b International Conference on Harmonization (ICH) [homepage on the Internet].  E6:  Good Clinical 
Practice:  Consolidated Guideline [finalized May 1996, corrected Jun 1996; cited 2005 Dec 06].  Available 
from: http://www.ich.org/cache/compo/276-254-1.html. 


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5) If new information becomes available that may influence the willingness of the 
subject to continue participation in the trial, the investigator or subinvestigator will 
promptly inform the subject of such information and confirm the willingness of the 
subject to continue participation in the trial, and then record the result in the subject’s 
medical records.  If there is guidance regarding the recording of re-consent stipulated 
by the trial site, it will be followed. 
 
13.3.2 
Contents of Informed Consent Form  
The informed consent form must explain the following: 
1) That the trial involves research 
2) The purpose of the trial 
3) The trial treatment(s) and the probability for random assignment to each treatment 
4) The trial procedures to be followed, including all invasive procedures 
5) The characteristics of HLA genotyping 
6) The subject's responsibilities 
7) Those aspects of the trial that are experimental 
8) The reasonably foreseeable risks or inconveniences to the subject and, when 
applicable, to an embryo, fetus, or nursing infant 
9) The reasonably expected benefits.  When there is no intended clinical benefit to the 
subject, the subject should be made aware of this. 
10) The alternative procedure(s) or course(s) of treatment that may be available to the 
subject, and their important potential benefits and risks 
11) The compensation and/or treatment available to the subject in the event of trial-related 
injury 
12) The anticipated prorated payment, if any, to the subject for participating in the trial 
13) The anticipated expenses, if any, to the subject for participating in the trial. 
14) That the subject's participation in the trial is voluntary and that the subject may refuse 
to participate or withdraw from the trial, at any time, without penalty or loss of 
benefits to which the subject is otherwise entitled. 
15) That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will 
be granted direct access to the subject's original medical records for verification of 
clinical trial procedures and/or data, without violating the confidentiality of the 
subject, to the extent permitted by the applicable laws and regulations and that, by 
signing a written informed consent form, the subject or the subject's legally acceptable 
representative is authorizing such access 
16) That records identifying the subject will be kept confidential and, to the extent 
permitted by the applicable laws and/or regulations, will not be made publicly 
available.  If the results of the trial are published, the subject’s identity will remain 
confidential. 


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17) That the subject or the subject's legally acceptable representative will be informed in a 
timely manner if information becomes available that may be relevant to the subject's 
willingness to continue participation in the trial 
18) The person(s) to contact for further information regarding the trial and the rights of 
trial subjects, and whom to contact in the event of trial-related injury 
19) The foreseeable circumstances and/or reasons under which the subject's participation 
in the trial may be terminated 
20) The expected duration of the subject's participation in the trial. 
21) The approximate number of subjects involved in the trial 
 
13.3.3 
Amendments to the Informed Consent Form  
If revision of the ICF becomes necessary due to newly obtained information, the 
investigator will promptly revise the ICF to include that information after conferring with 
the sponsor.   
The investigator, when revising the ICF, will report this to the head of the trial site and 
submit the revised document to the IRB designated by the trial site to obtain its approval. 
If new information becomes available that may influence the willingness of subjects to 
continue participation in the trial and the ICF has been revised according to the new 
information, the investigator or subinvestigator will again obtain subjects’ written 
informed consent to continue participation in the trial.  
13.4 
Management of Investigational Medicinal Products 
1) The sponsor will issue the “Procedures for Handling of Investigational Medicinal 
Products” to the head of the trial site and the IMP manager designated by the head of 
the trial site (referred to as the IMP manager hereinafter). 
2) The sponsor will issue the “Document on Investigational Medicinal Products Storage 
Conditions” to the investigator or subinvestigator, trial associates, and IMP manager. 
3) The sponsor will deliver the IMPs to the trial site following the start of the trial period 
contracted with the trial site. 
4) The IMP manager will manage the IMPs appropriately according to the “Procedures 
for Handling of Investigational Medicinal Products” prepared by the sponsor. 
5) The IMP manager will prepare and retain the “Record of Management and Storage of 
Investigational Medicinal Products.” 
 


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13.5 
Direct Access to Source Documents and Monitoring  
13.5.1 
Direct Access to Source Documents  
The head of the trial site and the investigator must accept monitoring and audits to be 
performed by the sponsor and inspection by the IRB and Japanese and foreign regulatory 
authorities, and must make source documents and all other trial-related records available 
to these agencies for direct access (including copying).  Subjects authorize such direct 
access by signing the written ICF. 
13.5.2 
Monitoring 
The sponsor bears responsibility for ethical, legal, and scientific conduct of the trial.  The 
sponsor will perform monitoring according to the “Procedures for monitoring” specified 
for this trial.  Monitoring includes periodic visits, phone calls, or other contact with the 
trial site for the provision, obtaining, and recording of updated trial-related information 
by monitors designated by the sponsor. 
The sponsor may entrust a portion of monitoring activity to a contract research 
organization. 
13.5.3 
Documents to Be Retained by the Investigator 
The trial-related documents to be retained by the investigator will be kept in the 
investigator’s file, which will be managed by the investigator. 
13.6 
Deviations From and Changes or Amendments to the Trial 
Protocol 
13.6.1 
Deviations From the Trial Protocol 
1) The investigator or subinvestigator should not deviate from the protocol or change it 
without prior written agreement between the investigator and the sponsor and the 
written approval of the IRB of the trial site based on prior review. 
2) In unavoidable medical circumstances such as the need to avoid emergent risk to a 
subject, the investigator or subinvestigator may deviate from the protocol or change 
the protocol without prior written agreement from the sponsor and prior approval of 
the IRB.  In such an event, the investigator will promptly submit a document 
providing the details of and reason for the deviation or change to the sponsor and the 
head of the trial site and obtain approval from the IRB.  In addition, the investigator 
will obtain written approval from the head of the trial site and the written agreement 
of the sponsor by way of the head of the trial site. 
3) The investigator or subinvestigator will record all deviations from the protocol.  
 


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13.6.2 
Amendments to the Trial Protocol  
1) The investigator will promptly submit to the sponsor, the head of the trial site, and the 
IRB by way of the head of the trial site, a written report on any changes in the trial 
that may significantly affect conduct of the trial or increase risks to the trial subjects. 
2) The sponsor, after conferring with the investigator, will agree with the investigator on 
the contents of the revised protocol and compliance with the revised protocol. 
3) The sponsor will promptly submit the revised protocol to the head of the trial site. 
 
13.7 
Archiving of Records 
1) The investigator and the trial site will retain all the trial-related documents and 
records for the period of time indicated in a) or b) below, whichever is longer.  
However, if the sponsor requires a longer period of archiving, the head of the trial site 
will consult with the sponsor on the period and procedures of record retention. 
a) A period of at least 3 years following the manufacturing and marketing approval 
of OCV-501; or, if the head of the trial site receives notification from the sponsor 
that development has been terminated or that results of the trial will not be 
submitted with the approval application, the date 3 years after receipt of such 
notification. 
b) The date 3 years after termination or completion of the trial. 
2) The investigator will retain the trial-related documents and records as directed by the 
head of the trial site. 
3) If it becomes no longer necessary to retain the trial-related documents and records at 
the trial site, the sponsor will notify the head of the trial site. 
 
13.8 
Termination or Interruption of Part or All of the Trial 
13.8.1 
Termination or Interruption of the Trial at Individual Trial Sites 
1) In the event of termination or interruption of the trial, the investigator will promptly 
provide the head of the trial site with written notification and a written explanation of 
the details of the termination or interruption of the trial. 
2) When the sponsor has been informed by the head of a trial site that the investigator 
has terminated or interrupted the trial, the sponsor will obtain a detailed written 
explanation of the termination or interruption of the trial from the head of the trial site. 
 
13.8.2 
Termination or Interruption of the Entire Trial 
1) When the entire trial is to be terminated or interrupted by the sponsor, the sponsor 
will promptly provide the heads of all trial sites involved in the trial and the 


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regulatory authority with written notification and a detailed written explanation of the 
reason for the termination or interruption of the trial. 
2) When the investigator has received notification of termination or interruption of the 
entire trial by the sponsor from the head of the trial site, the investigator will obtain a 
detailed written explanation of the termination or interruption of the trial from the 
head of the trial site, promptly notify the trial subjects currently receiving IMP 
administration, and take necessary measures such as switching to appropriate 
alternative treatment(s). 
3) When development of the IMP is terminated by the sponsor, the sponsor will 
promptly provide the heads and the investigators of all trial sites involved in the trial 
and the regulatory authority with written notification and a detailed written 
explanation of the reason for the termination of development. 
 
13.9 
Protection of Subjects’ Personal Information 
In completion and handling of CRFs, the investigator and subinvestigator will take 
adequate care to ensure protection of the personal information of subjects.  Individual 
subjects will be identified by subject numbers.  The sponsor will not provide the 
information obtained to any third party. 
As this trial will involve HLA genotyping, genetic information will be handled carefully 
and appropriately in consideration of the particularity of the information, even if it is not 
categorized as personal information due to being coded.  
13.10 
Compensation for Injury to Health 
Trial subjects will be compensated for health damages according to the criteria 
established by the trial sponsor with reference to applicable regional regulatory 
requirement(s) for this trial will comprise medical costs and medical benefits.   
13.11 
Agreement on Publication 
The sponsor may use the findings obtained from this trial for purposes such as an 
“Application for Approval of a Pharmaceutical Product” for the IMP. 
When the results of this trial and relevant data are to be published in scientific journals or 
at academic meetings, the investigator will obtain prior written approval from the sponsor. 


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14 
Trial Administrative Structure 
The administrative structure of this trial is shown in Annex 1, and Annex 2. 


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15 
Scheduled Duration of the Trial 
Sep 2013 through Dec 2017 


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16 
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Affairs and Communications and National Statistics Center:  from: http://www.e-
stat.go.jp/SG1/estat/eStatTopPortal.do 


Protocol No. 311-12-001 
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91 
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37 Kurosawa S. Comparison of post-remission strategies in elderly patients with acute 
myeloid leukemia in first complete remission, Rinsho Ketsueki. 2011;52(8):645-52. 
 

SAP_001.pdf: 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2 Trial to 
Evaluate the Efficacy and Safety of OCV-501 in Elderly Patients With Acute Myeloid 
Leukemia 
 
 
 
 
 
NCT Number: NCT01961882 
PRT NO.: 311-12-001 
Version Date: 09 January 2018 (Version 3.0) 


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Page 1 of 38 
PAREXEL International 
Otsuka Pharmaceutical Co., Ltd.  
Protocol No. 311-12-001  
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Evaluate 
the Efficacy and Safety of OCV-501 in Elderly Patients With Acute Myeloid Leukemia 
Statistical Analysis Plan 
PAREXEL Project Number: 210876 
Version 3.0 
Date: 09 Jan 2018 


Otsuka Pharmaceutical Co., 
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Statistical Analysis Plan 
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Table of Contents 
Table of Contents ........................................................................................ 4 
1 
INTRODUCTION .............................................................................. 8 
2 
TRIAL OBJECTIVES ....................................................................... 8 
3 
INVESTIGATIONAL PLAN ............................................................ 9 
3.1 
Overall Study Design and Plan ...........................................................................9 
3.1.1 
Screening Period ...............................................................................................9 
3.1.2 
Treatment Period ..............................................................................................9 
3.1.3 
Post-treatment Observation Period .................................................................10 
3.2 
Efficacy and Safety Variables ...........................................................................11 
3.2.1 
Efficacy ...........................................................................................................11 
3.2.2 
Safety ..............................................................................................................11 
3.2.3 
Exploratory variables ......................................................................................11 
4 
STATISTICAL METHODS ............................................................ 11 
4.1 
Data Quality Assurance .....................................................................................11 
4.2 
General Presentation Considerations.................................................................11 
4.3 
Study Subjects ...................................................................................................13 
4.3.1 
Disposition of Subjects ...................................................................................13 
4.3.2 
Protocol Deviations ........................................................................................14 
4.4 
Analysis Populations .........................................................................................14 
4.4.1 
Safety Analysis Set .........................................................................................14 
4.4.2 
Full Analysis Set .............................................................................................15 
4.4.3 
Per Protocol Set ..............................................................................................15 
4.4.4 
Immune Response Set .....................................................................................15 
4.5 
Demographic and Other Baseline Characteristics .............................................16 
4.6 
Treatment Compliance ......................................................................................17 
4.7 
Efficacy Evaluation ...........................................................................................18 
4.7.1 
Primary Efficacy Endpoints ............................................................................18 
4.7.1.1 
Disease-free Survival ..................................................................................18 
4.7.2 
Secondary Efficacy Endpoints ........................................................................20 
4.7.2.1 
Overall Survival ..........................................................................................20 
4.7.2.2 
Quality of Life .............................................................................................21 


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4.7.2.3 
Performance Status......................................................................................24 
4.7.3 
Reference Efficacy Endpoint ..........................................................................25 
4.7.3.1 
DFS until OS cutoff date .............................................................................25 
4.7.3.2 
Therapeutic Response .................................................................................26 
4.8 
Safety Evaluation ..............................................................................................26 
4.8.1 
Extent of Exposure .........................................................................................26 
4.8.2 
Adverse Events ...............................................................................................26 
4.8.3 
Clinical Laboratory Evaluation .......................................................................28 
4.8.4 
Vital Signs, Physical Findings and Other Observations Related to 
Safety ..............................................................................................................29 
4.9 
Safety Interim Analysis .....................................................................................30 
4.10 
Exploratory Items Analysis ...............................................................................30 
4.11 
Subgroup Analysis ............................................................................................31 
4.12 
Determination of Sample Size ...........................................................................31 
4.13 
Changes in the Conduct of the Study or Planned Analysis ...............................32 
5 
REFERENCES ................................................................................. 34 
DOCUMENT CHANGE RECORD......................................................... 35 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS 
 
Abbreviation 
Expansion 
AE 
Adverse event 
ADR  
Adverse drug reaction 
AML 
Acute myeloid leukemia 
AR(1) 
First-order autoregressive 
ATC 
Anatomic Therapeutic Chemical Classification 
CI 
Confidence interval 
CS 
Compound symmetry 
CSH 
Heterogeneous CS 
CTCAE 
Common Terminology Criteria for Adverse Events 
DFS 
Disease-free survival 
ECG 
Electrocardiogram  
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EORTC 
QLQ-C30 
The European Organization for Research and Treatment of Cancer QLQ-C30 
FAS  
Full analysis set 
HF 
Harrington-Fleming 
IFN-γ 
Interferon gamma 
HR 
Hazard ratio 
IRS 
Immune response set 
IMP 
Investigational medicinal product 
IVRS 
Interactive Voice Response Services 
IWRS 
Interactive Web Response Services 
LS 
Least squares 
MedDRA 
Medical Dictionary for Regulatory Activities (The ICH international medical 
dictionary) 
MMRM 
Mixed-effect model repeated measures 
OS 
Overall survival 
PPS 
Per protocol set 
PS 
Performance status 
PT 
Preferred term 
QTc 
Corrected QT interval 
QTcF 
QT interval as corrected by Fridericia’s formula 
QOL 
Quality of life 
REML 
Restricted maximum likelihood 
RS 
Raw score 
SAE 
Serious adverse event 
SD 
Standard deviation 
SOC 
System organ class 
SS 
Safety analysis set 
TOEP 
Toeplitz 


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Abbreviation 
Expansion 
UN 
Unstructured 
VC 
Variance Components 
WHO-DD 
World Health Organization Drug Dictionary 
WT1 
Wilm’s tumor gene 1 
 


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1 
INTRODUCTION 
OCV-501 is a drug product containing an HLA class II restricted Wilm’s tumor gene 1 
(WT1) derived peptide.  
In the phase 1 trial (Trial 311-10-001), OCV-501 was subcutaneously administered once 
a week for 4 times at doses of 0.3 mg, 1 mg, and 3 mg in elderly acute myeloid leukemia 
(AML) patients and safety and tolerability of OCV-501 were assessed. In this phase 1 
trial, no dose-limiting toxicities were reported and the tolerability of OCV-501 treatment 
up to a dose of 3 mg was confirmed. In addition, OCV-501 specific delayed-type 
hypersensitivity was observed at each dose. This finding suggests that OCV-501 induces 
the T cell mediated immune response. 
This trial is planned as a randomized placebo-controlled comparative trial, to assess the 
efficacy and safety of OCV-501 treatment as a maintenance therapy in elderly patients 
with AML who have completed consolidation therapy after being judged to have 
achieved complete remission following an induction regimen. 
This statistical analysis plan is based upon the following study documents: 
 Study protocol, 
 Electronic case report form (eCRF) 
 
2 
TRIAL OBJECTIVES 
The primary objective is to compare the disease-free survival (DFS) in AML patients 60 
years or older, who are randomly assigned to receive either OCV-501 monotherapy or 
placebo. 
The secondary objectives are:  
 To compare overall survival (OS) between both treatment arms 
 To compare patient quality of life (QOL) (European Organization for Research and 
Treatment of Cancer [EORTC] QLQ-C30) and performance status (PS; Eastern 
Cooperative Oncology Group performance status [ECOG PS]) between both 
treatment arms 
 To characterize and compare safety in both treatment arms 
 To assess immunological responses (OCV-501 specific interferon gamma [IFN-γ] 
production, WT1-killer peptide specific IFN-γ production, anti-OCV-501 antibody 
level, anti-WT1 antibody level, immunoglobulin) 
 To assess WT1 mRNA level 


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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
This trial is a multinational, multicenter, randomized, double-blind, placebo-controlled 
trial in elderly patients with AML, to compare DFS in patients 60 years or older with 
AML who are randomly assigned to receive either OCV-501 monotherapy or placebo. 
This trial consists of the following three periods. 
3.1.1 
Screening Period 
The eligible patients will be randomly assigned to one of the following treatment arms at 
a ratio of 1:1 
 OCV-501 arm: 3 mg of OCV-501 (0.4 mL)  
 Placebo arm: Placebo (0.4 mL)  
The patients will be assigned to either treatment arm via the interactive voice response 
services (IVRS) or the interactive web response services (IWRS). 
3.1.2 
Treatment Period 
From Week 1 to Week 104, the investigational medicinal product (IMP) will be 
subcutaneously administered: once-weekly up to the 8th administration, and every two 
weeks from the 9th administration onward.  
Blood sampling for expressed level of WT1mRNA, anti-OCV-501 antibody, anti-WT1 
antibody, and immunoglobulin will be performed at least once every four weeks. 
OCV-501 specific IFN-γ production, WT1-killer peptide specific IFN-γ production will 
be assessed at Week 5, Week 9, Week 13, and every 12 weeks.  
QOL and PS will be measured at least once every 4 weeks. A concomitant drug survey 
will be performed at every scheduled visit. For the safety of the subjects, a medical 
interview, blood biochemical tests, urinalysis, and adverse event (AE) observation will be 
performed. Vital signs, body weight, and 12-lead electrocardiogram (ECG) will be 
measured. 
Retrospective evaluation of samples will be conducted by the central pathological review 
committee. The central pathological review committee will evaluate the sample used at 
the judgment of relapse by the trial site and the previous sample from before relapse, and 
verify the judgment of relapse of the trial site. 
 


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3.1.3 
Post-treatment Observation Period 
Subjects will return to the trial site 11 to17 days after the last dose of the 2-year IMP 
administration period to undergo a completion examination during the post-treatment 
observation period. If a patient discontinues IMP administration before completion of the 
2-year treatment period, the patient will undergo a withdrawal examination within 7 days 
after the investigator or sub-investigator judged withdrawal to be necessary. 
The schedule of observations, examinations, and evaluations is shown in Table 3.1.3-1. 
 


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Table 3.1.3-1 
Trial Schedule 
Procedure 
  
Screening 
period 
 
Treatment period 
Post-treatment 
observation period *1 
W1 to W8 (once-weekly IMP administration) 
W9 to W104 (IMP administration every two weeks) 
Completion Withdrawal 
(Week) 
W1 
W2 
W3 
W4 
W5 
W6 
W7 
W8 
W9 
W11 
W13 
W15 After Week 17 up to 
Week 102 
W103 W104 11 - 17 days 
after W 103 
Within 7 
days from 
withdrawal 
judgment 
(Day) 
D1 
D8 
D15 
D22 
D29 
D36 
D43 
D50 
D57 
D71 
D85 
D99 
D715 
D722 
D279 
(Allowance) 
  
1 
5 - 11 12 - 18 19 - 25 26 - 32 33 - 39 40 - 46 47 - 53 54 - 60 66 - 76 80 - 90 
94 - 
104 
Same as W11 to W15 
（up to Week 102） 
710 - 
720 
- 
11-17 days 
after W 103 
Written informed consent 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Information 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virus test a) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest x-ray 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
hCG pregnancy test b) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body height 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient enrollment for this trial 
 
○ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for HLA 
genotyping 
 
○ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP administration c) 
 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ 
↓ (every 2 weeks) 
↓ 
 
 
 
(1) 
(2) 
(3) 
(4) 
(5) 
(6) 
(7) 
(8) 
(9) 
(10) 
(11) 
(12) 
(13-55) 
(56) 
 
 
 
Concomitant drug survey 
□ 
Adverse event observation 
□ 
Medical interview by (sub) 
investigator 
□ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ (every 2 weeks) 
○ 
 
□ 
□ 
Body weight 
□ 
▲ 
 
 
 
□ 
 
 
 
□ 
 
□ 
 
□ (every 4 weeks) 
 
 
□ 
□ 
Vital signs d) 
□ 
▲ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
Hematology test e) f) 
□ 
▲ 
 
○ 
 
○ 
 
○ 
 
○ 
○ 
○ 
○ 
○ (every 2 weeks) 
○ 
 
□ 
□ 
Peripheral blood smear 
preparation 
□ 
▲ 
 
□ 
 
□ 
 
□ 
 
□ 
□ 
□ 
□ 
□ (every 2 weeks) 
□ 
 
□ 
□ 
Blood biochemistry test g) 
□ 
▲ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
12-Lead electrocardiogram 
□ 
 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
 
 
□ 
□ 
QOL (EORTC QLQ-C30) 
 
○ 
 
 
 
□ 
 
 
 
□ 
 
□ 
 
□ (every 4 weeks) 
 
 
□ 
□ 
Performance status (ECOG PS) 
□ 
▲ 
 
 
 
□ 
 
 
 
□ 
 
□ 
 
□ (every 4 weeks) 
 
 
□ 
□ 
Bone marrow aspiration f) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
□ 
 
Bone marrow smear preparation g) 
□ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
□ 
 
Urinalysis h) 
□ 
▲ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
Expressed level of WT1mRNA 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
IFN-γ production (OCV-501 
specific, WT1-killer peptide 
specific) 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (at Weeks 25, 
37, 49, 61, 
73, 85, 97) 
 
 
□ 
□ 
Anti-501 antibody 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
○ (every 4 weeks) 
 
 
□ 
□ 
Anti-WT1 antibody 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
 
 
□ 
□ 
Immunoglobulin 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
○ 
 
 
 
□ 
□ 
●: Obtained before screening examinations. 
○: Mandatory (to be performed/collected before IMP administration). 
▲: Data from a screening examination can be used if they were obtained within 7 days before the IMP administration (to be performed before IMP administration except 
peripheral blood smear preparation). 
□: Mandatory 
a HIV antibody, HBV-DNA, HCV antibody. 
b To be performed only for female subjects who are capable of becoming pregnant (Urine test). 
c Once-weekly up to the 8th administration, once every two weeks from the 9th administration onward. The subject’s general conditions, including injection site reaction, 
must be observed at the trial site for one hour after IMP administration. 
d Blood pressure, pulse, body temperature 
e Hb, Hct, RBC, WBC, WBC differential (visual count), PLT. 
f If leukemic blast cells appear in peripheral blood or if there is a reduction in blood cell components, perform bone marrow aspiration by post-treatment observation period, 
and prepare smear. 
g AST, ALT, ALP, LDH, γ-GTP, TP, ALB, T-Bil, BUN,UA, Cr 
h pH and specific gravity, bilirubin, glucose, ketone bodies, white blood cells, occult blood, protein, urobilinogen 
* 1Even if treatment is discontinued before completion of the 2-year treatment period, patients will still undergo the post-treatment examination. 
(If an AE has not resolved by the end of the post-treatment observation period, the investigator or subinvestigator will explain to the subject the need for follow-up 
investigation and will request the subject’s cooperation. The investigator or subinvestigator will conduct a follow-up investigation within 4 weeks after the post-treatment 
observation period.) 


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3.2 
Efficacy and Safety Variables 
3.2.1 
Efficacy 
Primary endpoint: 
 
Disease-free survival (DFS) 
Secondary endpoint:    
 
Overall survival (OS) 
 
Quality of life (EORTC QLQ- C30) 
 
Performance status (ECOG PS) 
Reference endpoint: 
 
DFS until OS cutoff date 
3.2.2 
Safety 
AE, hematology tests, blood biochemistry tests, urinalysis, vital signs (blood pressure, 
pulse rate, body temperature), body weight and ECG 
3.2.3 
Exploratory variables 
OCV-501 specific IFN-γ production, WT1-killer peptide specific IFN-γ production, 
anti-OCV-501 antibody level, anti-WT1 antibody level, immunoglobulin and WT1 
mRNA level 
4 
STATISTICAL METHODS 
4.1 
Data Quality Assurance 
All tables, figures and data listings to be included in the report will be independently 
checked for consistency and integrity in accordance with standard PAREXEL 
procedures. 
4.2 
General Presentation Considerations 
The important terms will be defined as follows: 
 


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Term 
Definition 
Screen failure 
A screen failure is a subject from whom written informed consent was 
obtained, but to whom an IMP was not allocated 
Individual subject 
trial start date 
The day of obtaining the subject’s written informed consent 
Individual subject 
withdrawal 
A subject who discontinue OCV-501 or placebo treatment before 
completion of the post-treatment observation period 
Individual subject 
trial withdrawal date 
The day of the withdrawal examination of the post-treatment 
observation period within 7 days after the investigator or 
subinvestigator judged withdrawal to be necessary 
Individual subject 
completion 
A subject who complete 2 years of treatment with OCV-501 or 
placebo, and complete the post-treatment examination at 11-17 days 
after the end of IMP administration 
Individual subject 
trial completion date 
The day of the completion examination at 11-17 days after the end of 
the 2-year IMP administration period 
Individual subject 
trial period 
The period from the day of obtaining the subject’s informed consent 
to the day of trial completion or the day of the withdrawal 
examination. Does not include the follow-up period nor the outcome 
survey. 
 
Continuous data will be summarized in terms of the mean, standard deviation (SD), 
median, minimum, maximum and number of observations, unless otherwise stated. The 
minimum and maximum will be reported to the same number of decimal places as the 
raw data recorded in the database. The mean, median, lower quartile and upper quartile 
will be reported to one more decimal place than the raw data recorded in the database.  
The SD will be reported to two more decimal places than the raw data recorded in the 
database. In general, the maximum number of decimal places reported shall be four for 
any summary statistic. 
Categorical data will be summarized in terms of the number of subjects providing data at 
the relevant time point, frequency counts and percentages. Percentages will be presented 
to one decimal place. Percentages will not be presented for zero counts. Percentages will 
be calculated using the number of observations with non-missing values as the 
denominator.     
Changes from baseline in categorical data will be summarized using shift tables where 
appropriate. 


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P-values greater than or equal to 0.001, in general, will be presented to three decimal 
places. However, if a p-value is only presented to four decimal places (by SAS) it will not 
be rounded again, but will be presented to four decimal places.  P-values less than 0.001 
will be presented as “<0.001”. 
Two sided statistical tests with =0.05 will be performed to test the hypotheses. 
95% Confidence intervals (CIs) will be presented to one more decimal place than the raw 
data. Multiplicity will not be adjusted.  
All report outputs will be produced using SAS® version 9.3 or a later version in a secure 
and validated environment. 
Baseline 
Baseline is defined as the last available screening or pre-treatment assessment. 
Allowance window 
Assessments taken outside of protocol allowable windows will be included in the 
summaries according to the eCRF assessment recorded by the investigator. 
Unscheduled assessments 
Extra assessments (laboratory data, vital signs or exploratory items associated with 
non-protocol clinical visits or obtained in the course of investigating or managing AEs) 
will be included in listings but not summaries.  
Discontinuation assessments 
Discontinuation assessments will be summarized according to the eCRF assessments 
recorded by the investigator at the time of discontinuation, not otherwise specified. 
Graphs 
Graphs will be plotted by “day” or “month” or “Visit timepoint (week)” as specified in 
the shells.  
 
4.3 
Study Subjects 
4.3.1 
Disposition of Subjects 
A clear accounting of the disposition of all subjects who enter the study from screening to 
study completion will be generated. 
The following summaries will be generated. 


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 A summary of subjects with informed consents, screen failure subjects by reasons, 
subjects randomized, entering and discontinuing each period (week 1-8, week 9-104 
and post-treatment), subjects completed the study and discontinued subjects (Analysis 
population: all subjects with informed consents) 
 A summary of the number of subjects randomized per site and per country/region 
(Analysis population: all subjects randomized) 
 A summary of subjects treated (with at least one IMP administration), subjects 
completed the study and discontinuations from the study with major reasons. 
(Analysis population: all subjects randomized) 
 
4.3.2 
Protocol Deviations 
The protocol deviation summaries may include the following: 
 
A summary of subjects with major protocol deviation in each country/region and site 
by treatment arm and overall and by type of deviation (Analysis population: all 
subjects randomized) 
 
A summary of the number and percentage of subjects with major deviations 
(Inclusion/Exclusion Criteria, Withdrawal Criteria, IP administration/Study treatment, 
Disallowed Medication) 
 
A by-subject listing of major or minor protocol deviations will be generated. 
 
4.4 
Analysis Populations 
In this study, 4 analysis populations are employed, and the definitions are described in the 
following section. The analysis population summaries include the following: 
 
A summary of the number and percentage of subjects by treatment arm for each 
analysis population will be generated. 
 
A by-subject listing of analysis population details (site, subject ID 
inclusion/exclusion flag for each population and reason for exclusion from each 
population) will also be generated. 
 
4.4.1 
Safety Analysis Set  
The safety analysis set (SS) includes all subjects who have received the IMP at least once 
and from whom data on at least one safety endpoint was obtained after the start of IMP 
administration. 


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If subjects have received the wrong IMP administration other than the one that they were 
originally randomized into, then they will be analyzed as “As treated”. 
 
4.4.2 
Full Analysis Set  
The full analysis set (FAS) includes all subjects who received the IMP at least once and 
from whom data on at least one efficacy endpoint was obtained after the start of IMP 
administration. 
If the subjects receive the wrong IMP administration, then they will be analyzed as “As 
randomized”. 
 
4.4.3 
Per Protocol Set  
The per protocol set (PPS) includes all FAS subjects except those who have major 
protocol deviations or those who have withdrawn from the trial within 8 weeks from start 
of IMP administration. However, if a subject withdrew due to any reason other than an 
event (relapse or death) within 8 weeks from start of IMP administration, the subject will 
still be included in the PPS. 
Subjects with the following major protocol deviations are excluded from PPS. 
 
Inclusion/Exclusion Criteria 
 
Compliance deviations (Patients do not receive the IMP at least 2 times up to the 8th 
administration or compliance rate is less than 80% throughout the period.) 
 
Disallowed medications 
 
Withdrawal Criteria 
If the subjects receive the wrong IMP administration, then they will be analyzed as “As 
randomized”. 
 
4.4.4 
Immune Response Set  
The immune response set (IRS) includes all subjects who received the IMP at least once 
and from whom data on at least one immune response endpoint were obtained after the 
start of IMP administration. 


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CONFIDENTIAL 
Project Document Version No. 3.0 
Effective Date:  25 Nov 15 
Project Document Effective Date: Date of last signature  
Related to:  SOP-GDO-WW-019 
 
Page 16 of 38 
 
If the subjects receive the wrong IMP administration, then they will be analyzed as “As 
treated”. 
 
4.5 
Demographic and Other Baseline Characteristics 
1) Definition: 
Demographic: 
Age, sex, height, body weight (at screen), race, trial country/region 
Age will be divided into 3 groups (60 to 64 years, 65 to 70 years, ≥ 71 years). 
Underlying diseases, induction/consolidation therapy and other baseline factors 
Diagnosis of AML (WHO classification), duration from the last dose of consolidation 
therapy to randomization, duration from diagnosis of AML to randomization, regimen of 
number and therapy (induction, consolidation), WT1 mRNA level at Day 1, unfavorable 
karyotype abnormality (abn(3q)/inv(3)/t(3;3) or -5/del(5q) or -7/del(7q) or t(6;9)), 
cytogenetic abnormality (FLT3-ITD mutation) 
WT1 mRNA level (copy/ugRNA) will be divided into 4 categories (<50, 50-199, 200<= 
and Unknown). 
Prior and concomitant drugs/treatments 
Prior and concomitant medications will be classified by Anatomic Therapeutic Chemical 
Classification 2 (ATC2) and generic (preferred) name using World Health Organization 
Drug Dictionary (WHO-DD). 
The start or stop dates of administration of drugs/treatments other than IMP will be 
compared to the date of first IMP administration to classify them as either prior or 
concomitant drugs/treatments.  
Table 4.5-1 
Prior and Concomitant Drugs/Treatments 
Prior  
Stop date of drug/treatment  First IMP administration date 
Concomitant Stop date of drug/treatment > First IMP administration date 
 
Concomitant drugs/treatments starting after the completion/withdrawal date will be listed 
but will not be classified or summarized. 
Medical history and Concomitant disease 
Medical history and concomitant disease are coded using Medical Dictionary for 
Regulatory Activities (MedDRA version 20.1). If the condition is not continuing at the 


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Statistical Analysis Plan 
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time of informed consent, it is considered as medical history. If the condition is 
continuing, then it is concomitant disease. 
2) Analysis Set: 
FAS, PPS, SS, IRS 
3) Analysis Method: 
Frequency counts and percentage or descriptive statistics for each variable will be 
calculated according to the nature of the data (continuous or discrete) by treatment arm 
and overall. For WT1 mRNA level, the measurement “<50” will be translated into 49 
when calculating descriptive statistics. 
The following summaries will be generated. 
 A summary of demographic variables at baseline by treatment arm and over all 
 A summary of other baseline characteristics by treatment arm and overall 
 Subgroup analysis (Age, Country/Region) of demographic characteristics (FAS only) 
 Subgroup analysis (Age, Country/Region) of other baseline characteristics (FAS 
only) 
 A summary of prior and concomitant drugs/treatments (WHO drug terms) by 
treatment arm and overall (FAS only) 
 A summary of Medical history by System Organ Class (SOC) and Preferred Term 
(PT) by treatment arm and overall (FAS only) 
 A summary of Concomitant disease by SOC and PT by treatment arm and overall 
(FAS only) 
 
4.6 
Treatment Compliance 
1) Definition: 
 Treatment compliance will be calculated as 
         
100
(%)


IMP
of
number
Scheduled
IMP
of
number
Actual
ompliance
Treatmentc
, 
Where the scheduled number of IMP administrations is the number scheduled 
until the time of withdrawal. 
2) Analysis Set: 
SS 
3) Analysis Method: 


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A summary of the descriptive statistics will be calculated by treatment arm. Compliance 
rates (%) will be divided into 6 categories (<20, 20 - <40, 40 - <60, 60 - <80, 80 - <100, 
100). The following outputs will be generated. 
 A summary of IMP exposure by compliance rate 
 A by-subject listing of treatment compliance data  
 
4.7 
Efficacy Evaluation 
FAS will be used as the primary analysis population and PPS will be used as the 
secondary analysis population to evaluate the stability. 
 
4.7.1 
Primary Efficacy Endpoints 
4.7.1.1 
Disease-free Survival  
1) Definition: 
 Observation period: For each subject, the time from randomization to the DFS- 
cutoff date.  The DFS-cutoff date was set as the completion/discontinuation date 
of each subject. 
 DFS: The time from randomization until relapse or death from any cause, 
whichever comes first by the DFS-cutoff date. 
 Event: Relapse or death from any cause by the DFS-cutoff date. 
 Censoring:  
 If an event has not been observed by the DFS-cutoff date, then the last 
confirmed non-relapse date will be used as the censoring date. 
 For subjects who have withdrawn from this trial before the completion 
date for reasons other than relapses or deaths, if non-relapse has been 
confirmed on the withdrawal date, then the withdrawal date will be 
used as the censoring date. Otherwise, the last confirmed non-relapse 
date will be used as the censoring date. 
2) Analysis Set: 
FAS (primary), PPS 
For the judgment of relapse by the central pathological review committee, DFS will be 
evaluated in the FAS and PPS as primary analysis.  
For the judgment of relapse by trial site, DFS will only be evaluated in the FAS as 
secondary analysis. 
3) Analysis Method: 


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 Primary test for comparison between OCV-501 and Placebo will be conducted by 
Log-rank test. For exploratory purposes, the Harrington-Fleming (HF) test will be 
performed by applying the weight 1- Ŝ(t), where Ŝ(t) is the product-limit estimates of 
survival functions. 
 Kaplan-Meier estimate of survivor function Ŝ(t) and curve 
        Ŝ(t) = Pr (Survive beyond t) 
           










t
t
j
j
j
j
j
n
y
n
:
 
where tj is the j-th event time, nj is the number of patients at risk and yj is the number 
of events. 
The Kaplan-Meier curve plots the estimated survival function Ŝ(t) vs. time separately for 
each treatment arm. 
 The 2-year survival rate and median survival time will be calculated. The 95% CI of 
the 2-year survival rate will be calculated using Greenwood formula. 
 Hazard ratio (HR) and its 95% CI will be calculated from the Cox proportional 
hazards model. 
- In the model of Cox analysis, treatments effect will be adjusted with covariates 
(Age, Country/Region and WT1 mRNA level at Day 1). The model with covariates 
(WT1 mRNA only) or model without covariates will be also analyzed. In these 
models, age will be categorized into 3 groups (60 to 64 years, 65 to 70 years, ≥ 71 
years), Country/Region into 2 groups (Japan, Republic of Korea+Taiwan), WT1 
mRNA into 4 groups (<50, 50-199, 200<= and Unknown). 
- BRESLOW method will be used for ties.  
- Proportionality assumption in Cox proportional hazard model will be assessed 
using 2 methods: 
1) 
SAS PHREG procedure ASSESS PH option will be used for checking 
proportional hazard assumption.  
2) 
Look at the log-minus-log survival plots graphically. If the graph results in 
parallel lines then the proportionality assumption is satisfied.    
 
HR and its 95% CI at every 3 months interval will be calculated by adding a time 
varying covariate to Cox Proportional Hazards model as an alternative analysis if the 
proportionality assumption fails.  The model will be as follows: 
λ(t;X) =λ0(t) exp(1trt*period_1+ 2trt*period_2+.....)  
where λ0(t) is the baseline hazard function,  


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      trt is the treatment arm(1= OCV-501 and 0= Placebo) and 
      






otherwise
Months
time
DFS
if
period
0
3
0
1
1
_
 
      






otherwise
Months
time
DFS
if
period
0
6
3
1
2
_
         
 
 
 So HR (OCV-501 vs. Placebo) for each period will be calculated as follows: 
λ(OCV-501|period_k)= λ0(t)exp(k) 
λ(Placebo|period_k)= λ0(t) 
HR(OCV-501 vs. placebo|period_k)= λ0(t)exp(k)/ λ0(t)= exp(k) 
95% CI :[exp(k-1.96*
))
(
k
Var 
, exp(k+1.96*
))
(
k
Var 
] 
 
For exploratory purposes, the incidence rate over the entire follow-up period will be 
calculated using the person-year method by treatment arm as follows. 
1) Calculate the number of events and person-year at risk by treatment arm. 
2) Calculate the incidence rates and its corresponding 95% CI by treatment arm. (1 
year is calculated as 365.25 days) 
Rate= 
year
Person
events
of
Number

 
95% CI:  
[Rate/exp(1.96*
events
of
Number
1
), Rate* exp(1.96*
events
of
Number
1
)] 
 
4.7.2 
Secondary Efficacy Endpoints 
4.7.2.1 
Overall Survival  
1) Definition: 
 Observation period: For all subjects, the time from randomization to OS-cutoff 
date. The OS-cutoff date was set as the date after 728 days (2 years) from the day 
that the last subject started IMP administration without consideration of 
withdrawal by the OS-cutoff date. 


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 Definition: The time from randomization until death from any cause by the 
OS-cutoff date. 
 Event: Death from any cause by the OS-cutoff date. 
 Censoring: If an event has not been observed by the OS-cutoff date, then the last 
confirmed survival date will be used as the censoring date. 
2) Analysis Set: 
FAS, PPS 
3) Analysis Method: 
The same analysis will be conducted as for DFS. 
4.7.2.2 
Quality of Life  
1) Based on the scoring rule (EORTC QLQ-C30 version 3), the following scales and 
single items will be calculated and analyzed. 
Table 4.7.2.2-1 
Quality of Life Scale 
Global health status / QOL 
Functional Scale:  Physical, Role, Cognitive, Emotional, Social  
Symptom Scale: Fatigue, Pain, Nausea/Vomiting  
Single Items: Dyspnea, Sleep disturbance, Appetite loss, Constipation, Diarrhea, 
Financial impact 
 
Scoring rule13: 
The QLQ-C30 is composed of both multi-item scales and single-item measures. These 
include 5 functional scales, 3 symptom scales, a global health status/QOL scale, and 6 
single items. Each of the multi-item scales includes a different set of items - no item 
occurs in more than one scale. 
-  All of the scales and single-item measures range in score from 0 to 100.  
-  A high scale score represents a higher response level. Thus a high score for a 
functional scale represents a high/healthy level of functioning, a high score for the global 
health status/QOL represents a high QOL, but a high score for a symptom scale/item 
represents a high level of symptomatology/problems. 
Scoring principle: 
1) Estimate the average of the items that contribute to the scale; this is the raw score 
(RS). 


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2) Use a linear transformation to standardize the RS, so that scores range from 0 to 
100; a higher score represents a higher ("better") level of functioning, or a higher 
("worse") level of symptoms 
 
Technical summary: 
In practical terms, if items I1, I2,.... , In are included in a scale, the procedure is as follows: 
Raw score (RS) 
Calculate the RS: 
 Raw score = RS=
n
I
I
 
I
n
2
1



 
Linear transformation 
Apply the linear transformation to 0-100 to obtain the score S 
Functional scales:  S=
100
)1
(
1








Range
RS
 
Symptom scales / items: S= 
100
)1
(








Range
RS
 
Global health status / QOL:  S= 
100
)1
(








Range
RS
 
- Range is the difference between the maximum possible value of RS and the minimum 
possible value. The QLQ-C30 has been designed so that all items in any scale take the 
same range of values.  Therefore, the range of RS equals the range of the item values. 
Most items are scored 1 to 4, giving range = 3.  
- The exceptions are the items contributing to the global health status/QOL, which are 
7-point questions with range = 6, and the initial yes/no items on the earlier versions of 
the QLQ-C30 which have range = 1. 
2) Analysis Set: 
FAS, PPS 
3) Analysis Method: 
 A summary of descriptive statistics of each score will be calculated by treatment arm. 


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 Mixed-effect model repeated measures (MMRM) will be performed with treatment as 
fixed effect.  
 The dependent variable is the change from baseline to each visit in each scale of QOL 
score. The model will include treatment arm, protocol-specified visit, and 
treatment-by-visit interaction.  
 Changes from baseline at each time point will be plotted in trend diagrams. The 
difference of Least square (LS)-means and CI between two treatment arms will also 
be generated. 
- The primary hypothesis test is the test of the difference of LS-means between treatment 
arms over time.  
- The mixed model is as follows: 
Y = Xβ + Zu + ε 
- A key assumption is that u and ε are normally distributed with 
          E









0
0

u
  and Var









R
G
u
0
0

 
- The mean will be modeled as E[Y]= Xβ and the variance will be modeled as Var [Y] = 
ZGZ’ + R.  Therefore, the variance of Y can be modeled by setting up the structure of 
G and R. 
- The covariance structure will be assumed to be UN. It could be switched from UN to 
TOEP (Toeplitz), CSH (Heterogeneous Compound Symmetry), AR(1) 
[(Autoregressive(1)], CS (Compound Symmetry) and VC (Variance Components) in 
this order if convergence is not achieved.  
- Restricted maximum likelihood (REML) will be used to make the inference. 
- All analyses will be performed on the observed data. 
- Discontinuation assessment will be analyzed using the following allowance window.  
If two values fall into the same visit window, then the latter will be taken into analysis. 
Week 
Target Daya 
Study Day Intervala 
1(Baseline) 
1 
-7 
- 
1 
5 
29 
2 
- 
43 
9 
57 
44 
- 
71 
13 
85 
72 
- 
99 
17 
113 
100 
- 
127 
21 
141 
128 
- 
155 
25 
169 
156 
- 
183 
29 
197 
184 
- 
211 


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33 
225 
212 
- 
239 
37 
253 
240 
- 
267 
41 
281 
268 
- 
295 
45 
309 
296 
- 
323 
49 
337 
324 
- 
351 
53 
365 
352 
- 
379 
57 
393 
380 
- 
407 
61 
421 
408 
- 
435 
65 
449 
436 
- 
463 
69 
477 
464 
- 
491 
73 
505 
492 
- 
519 
77 
533 
520 
- 
547 
81 
561 
548 
- 
575 
85 
589 
576 
- 
603 
89 
617 
604 
- 
631 
93 
645 
632 
- 
659 
97 
673 
660 
- 
687 
101 
701 
688 
- 
715 
105 
729 
716 
- 
743 
a. Relative to the first day of IMP taken in treatment phase (Date of first IMP taken is defined as the Day 1) 
 
4.7.2.3 
Performance Status  
1) Definition: Performance status (PS) will be scored according to the following criteria. 
Table 4.7.2.3-1 
Performance Status Grade 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g, light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
 
2) Analysis Set: 
FAS, PPS 
3) Analysis Method: 
 Frequency distributions of PS scores at the baseline and each post-baseline time point 
(including completion/discontinuation) will be calculated by treatment arm. 


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 Shift table of PS scores by grade at baseline and the end of trial will be generated by 
treatment arm.  
 PS will be compared at the time of completion or discontinuation based on the 
improvement factor, which will be defined as follows. 
Table 4.7.2.3-2 
Improvement Factor 
Improvement factor 
Definition 
Better 
Current PS score < Baseline PS score 
No change 
Current PS score = Baseline PS score 
Worse 
Current PS score > Baseline PS score 
- To compare the treatment effect in PS improvement factor between treatment arms, 
Wilcoxon 2-sample test will be carried out. 
 
4.7.3 
Reference Efficacy Endpoint 
4.7.3.1 
DFS until OS cutoff date 
1) Definition: 
 Observation period: For all subjects, the time from randomization to OS cutoff 
date  
 DFS for reference: The time from randomization until relapse or death from any 
cause, whichever comes first, by the OS cutoff date 
 Event:  
Relapse or death from any cause, whichever comes first by the OS cutoff date 
 Censoring: 
 If an event has not been observed by the OS cutoff date, the last confirmed 
non-relapse date will be used as the censoring date. 
 For subjects who have withdrawn from this trial before the OS cutoff date for 
reasons other than relapse or death, if non-relapse has been confirmed on the 
withdrawal date, then the withdrawal date will be used as the censoring date. 
Otherwise, the last confirmed non-relapse date will be used as the censoring 
date. 
2) Analysis Set: 
For the judgment of relapse by trial site, DFS will only be evaluated in the FAS. 
3) Analysis Method: 
The same analysis method will be conducted as for DFS.  


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4.7.3.2 
Therapeutic Response 
1) Definition: 
Relapse will be assessed according to the response criteria of the International 
Working Group shown in the protocol, Table 7.2.1.1-1. Relapse will be judged by the 
investigator in the site (Site judgment) and by Central Pathological Reviewer (Central 
judgment) and recorded in eCRF. 
2) Analysis Set: 
FAS, PPS  
3) Analysis Method: 
 
A summary of the number and percentage of subjects judged as Relapse by both 
Central judgment and Site judgment will be calculated. 
 
4.8 
Safety Evaluation 
4.8.1 
Extent of Exposure  
1) Definition: 
Duration of exposure to treatment (days), full dose of OCV-501, total number of doses 
2) Analysis Set: 
SS 
3) Analysis Method: 
A summary of the descriptive statistics will be calculated by treatment arm. 
Duration of exposure to treatment will be calculated in days as follows: 
IMP administration end date − IMP administration start date + 1 
 
4.8.2 
Adverse Events 
1) Definition: 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA 
version 20.1). Severity will be graded using Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.03. 


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Treatment-emergent AEs (TEAE) are defined as those AEs that either start or worsen in 
severity on or after the date/time of first dose of IMP administration. TEAEs will be 
tabulated by SOC and PT with PT substituted for verbatim terms. 
An adverse drug reaction (ADR) is defined as a response to a drug which is noxious and 
unintended, and which occurs at doses normally used in man for the prophylaxis, 
diagnosis, or therapy of disease, or for the modifications of physiological function (WHO 
definition). In this study, AEs with causal relationship (Definitely related, Probably 
related, Possibly related) are considered as ADR (potentially drug related AEs). 
When dates are missing or partially missing, AEs will be assumed to be 
treatment-emergent, unless there is clear evidence to suggest that the AE started prior to 
the first dose of IMP administration. 
Also, serious adverse event (SAE), death and AE leading to discontinuation will be 
considered separately.  
2) Analysis Set: 
SS 
3) Analysis Method: 
All TEAE summaries will describe the number of subjects reporting at least one AE and 
the total number of events reported. These will generally include the following 
summaries: 
 A summary of the number and percentage of subjects reporting a TEAE or ADR by 
treatment arm, SOC and PT 
 A summary of the most common TEAEs or ADRs by treatment arm, SOC and PT 
(reported by 5% of subjects in any treatment arm) 
 A summary of the TEAEs by treatment arm and PT (reported by 5% of subjects in 
any treatment arm) 
 A summary of the number and percentage of subjects reporting a TEAE or ADR by 
treatment arm, CTCAE severity grade, SOC and PT 
 A summary of the number and percentage of subjects reporting a TEAE by maximum 
CTCAE grade and PT (Category: All grade, Grade 1+2, Grade 3+4+5) 
 A summary of the number and percentage of subjects reporting a TEAE or ADR 
leading to death by treatment arm, SOC and PT 
 A summary of the number and percentage of subjects reporting a serious TEAE by 
treatment arm, SOC and PT 


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 A summary of the number and percentage of subjects reporting a TEAE or ADR 
leading to discontinuation by treatment arm, SOC and PT 
 A summary of all the summaries above 
For by-severity summaries, for each subject reporting multiple AEs, the worst severity 
recorded will be used. 
By-subject listings of all AEs (including non-treatment-emergent events) will be 
generated. These will include the following. 
 A by-subject listing of all deaths that occurred during the study 
 A by-subject listing of all SAEs other than death 
 A by-subject listing of all AEs leading to discontinuation of IMP administration 
 
4.8.3 
Clinical Laboratory Evaluation 
1) Definition: 
A subject will be defined as having a treatment-emergent laboratory abnormality if any of 
the following conditions are satisfied for a specific laboratory parameter. 
 A laboratory result within the normal range at baseline and either a result below the 
lower limit of the normal range or above the upper limit of the normal range at any 
post-baseline time point. 
 A laboratory result below the lower limit of the normal range at baseline and a 
laboratory result above the upper limit of the normal range at any post-baseline time 
point. 
 A laboratory result above the upper limit of the normal range at baseline and a 
laboratory result below the lower limit of the normal range at any post-baseline time 
point. 
 
In addition, laboratory values will be graded using CTCAE version 4.03. 
 
2) Analysis Set: 
SS 
3) Analysis Method: 
The following summaries will be generated: 
 A summary of each laboratory parameter and its change from baseline by treatment 
arm and time point 


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 Shift table of laboratory parameter (Urinalysis) at each post-baseline point 
 A summary of the number and percentage of subjects experiencing low, normal and 
high values at baseline and at each post-baseline time point (shift table) 
 A summary of the number and percentage of subjects with different CTCAE grades at 
baseline, at each post-baseline time point and worst grade in post-baseline (shift 
table) 
 A summary of new or worsened laboratory abnormalities based on CTCAE Grades 
(Categories: all grades, Grade 1+Grade 2, Grade 3+Grade 4) 
In this table, the worst grade observed in post-baseline are summarised. Patients with 
no change or better grade from baseline are not counted. ‘New’ abnormality means 
‘grade 0’ at baseline and ‘>= grade 1’ after baseline. All grade means ‘>= grade 1’ 
after baseline. 
By-subject listings of all laboratory data will be generated by treatment arm with 
reference range provided and abnormal values will be marked with flags (H/L, Gx).  
 
4.8.4 
Vital Signs, Physical Findings and Other Observations Related 
to Safety 
1) Definition: 
Vital signs (blood pressure, pulse rate, body temperature), body weight and ECG.  
ECG parameters will include heart rate, PR interval, QRS complex, QT interval and QTc 
interval. 
2) Analysis Set: 
SS 
3) Analysis Method 13: 
The following summaries will be generated: 
 A summary of each vital signs, body weight and ECG and its change from baseline 
by treatment arm and time point. 
 A summary of the number and percentage of subjects having QTcF interval values  
> 450 ms, > 480 ms and > 500 ms at each time point. 
 A summary of the number and percentage of subjects having QTcF interval changes 
from baseline > 30 ms and > 60 ms at each post-baseline time point. 
 Shift table of 12-Lead ECG findings at each post-baseline time point and worst in 
post-baseline assessment 


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By-subject listings of vital sign parameters and ECG results will also be generated.  
4.9 
Safety Interim Analysis 
For the purpose of data safety monitoring, the safety interim analysis will be conducted 
regularly on all subjects while the level of blinding is being maintained. 
The following summaries will be generated.  
 A summary of patient background  
 A summary of treatment compliance (overall and until withdrawal) 
 A summary of number and percentage of subjects reporting a TEAE by SOC and PT 
 A summary of number and percentage of subjects reporting a TEAE by CTCAE 
severity grade, SOC and PT 
The following by-subject listings will be generated. 
 A by-subject listing of all SAEs other than death 
 A by-subject listing of all deaths 
 
Also, the following graphs will be generated. 
 Kaplan-Meier curve of DFS 
 Kaplan-Meier curve of OS 
 
4.10 Exploratory Items Analysis  
1) Definition: 
OCV-501 specific IFN-γ production, WT1-killer peptide specific IFN-γ production, 
anti-OCV-501 antibody level, anti-WT1 antibody level, WT1 mRNA level and 
immunoglobulin 
2) Analysis Set: 
IRS 
3) Analysis Method: 
Generally, a summary will be calculated in terms of the mean, geometric mean, SD, 
coefficient of variation, median, minimum, maximum and number of patients, unless 
otherwise stated.  
At each time point, a summary of each exploratory parameter and change from baseline 
will be generated and time courses of immune response values will be plotted by 
treatment arms.  


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4.11 Subgroup Analysis 
1) Definition: 
DFS, OS, safety (Summary of TEAE, TEAE by MedDRA SOC and PT) and exploratory 
parameters will be examined for the following subgroups. 
 
Table 4.11-1 
Subgroup 
Factor 
Categories 
Country/ Region 
Japan, Republic of Korea, and Taiwan 
Age 
60 to 64 years, 65 to 70 years, ≥ 71 years 
 
2) Analysis Set: 
FAS for DFS and OS, SS for safety, IRS for Immune response  
3) Analysis Method: 
For each subgroup, the following statistical analyses will be performed.  
DFS/OS: log-rank test, HF test, KM estimates of DFS/OS rate 
Safety: Summary of TEAE, Incidences of TEAE by MedDRA SOC and PT 
Exploratory parameters: Summary of descriptive statistics 
 
4.12 Determination of Sample Size 
The number of AML patients is not very high, and is estimated to be approximately 7000 
in Japan7. From the fact that in the previous clinical trial (JALSG GML200) in elderly 
AML patients, it has been forecast that the possible enrollment in Japan is to be at most 
70 in one year. Also, from the preliminary trial feasibility survey, it is known that around 
50 subjects could be recruited in one year in the Republic of Korea and Taiwan. Through 
a global trial in Japan, the Republic of Korea and Taiwan, it is considered possible to 
enroll 120 subjects in one year to assess the efficacy of OCV-501.   
Within the limitation of the past experiences with regard to IMP administration, the target 
sample size will be considered with reference to following publications.5,6,7,9   With 
reference to disease-free survival which has been reported from trials in AML patients 60 
years or older who have received the consolidation therapy followed by maintenance 
therapy, the 2-year DFS rate of placebo arm has been estimated to be around 20%.5,6,7 


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On the other hand, considering the so-called graft-versus-leukemia (GVL) effect 
associated with a lower relapse risk after the allogeneic hematopoietic stem cell 
transplantation, OCV-501 is basically expected to have the same benefits. With reference 
to the findings of Kurosawa et al,9 which have reported a 30% higher 2 or 3-year DFS in 
elderly AML subjects who have received the allogeneic hematopoietic stem cell 
transplantation compared with those without transplantation, OCV-501 is expected to 
have a 15% - 20% higher 2-year DFS. Under the assumption of exponential distribution 
of DFS time, the hazard ratio (placebo vs. OCV-501) has been set to 0.57 - 0.65, and with 
a two-sided log-rank test at the 5% significance level, 60 or more subjects in each 
treatment group can achieve a power of 53% - 75% or more to detect the difference 
between placebo and OCV-501 groups.  
 
4.13 Changes in the Conduct of the Study or Planned Analysis 
Any changes made after the database lock will be recorded in the relevant section of the 
clinical study report. 
Changes from the analysis planned in the protocol are as follows: 
Section number 
Contents of changes 
Reason of changes  
4.5 Demographics and 
Other Basic 
Characteristics 
WT1 mRNA level at Day 1 
was added instead of AML 
diagnosis or at the time of 
induction therapy or 
consolidation therapy. 
Day 1 data would be 
more influential than the 
data at diagnosis or at the 
time of induction or 
consolidation therapy. 
4.7.1.1 DFS  
4.7.2.1 OS  
Proportionality assumption 
will be tested first. Cox PH 
model will be conducted on 
every 3 month interval as an 
alternative analysis. 
If proportionality 
assumption fails, then 
Cox PH model might be 
considered invalid to 
conduct on the whole 
period. 
 
 


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Section number 
Contents of changes 
Reason of changes  
4.7.1.1 DFS  
4.7.2.1 OS 
Age, country and other 
factor (WT1 mRNA) will 
be adjusted as covariates in 
the Cox PH model. 
Furthermore, subgroup 
analysis will be conducted.  
Cox PH model analyses 
adjusted by covariates are 
added to investigate the 
influence of covariates. 
And the subgroup 
analyses are added as 
supplementary analyses. 
4.7.2.2 QOL  
Mixed-effect model 
repeated measures will be 
conducted. 
To make a comparison on 
QOL between two 
treatment arms.  
4.7.2.3 PS  
Improvement factor will be 
created and Wilcoxon 
2-sample test will be 
conducted.  
To make a comparison on 
PS between two 
treatment arms.  
4.7.3. Reference efficacy 
endpoint 
4.7.3.1 DFS until OS 
cutoff date 
4.7.3.2 Therapeutic 
Response 
New efficacy variables have 
been added. 
For the purpose of 
reference 
4.8.2 Adverse Events 
A summary of SAEs by 
severity is not conducted. 
Listing will cover it. 
4.10 Exploratory Items 
Analysis 
For WT1 mRNA item, t-test 
is not conducted. 
According to the nature 
of WT1mRNA data, 
comparison between 
treatment arms will not 
be necessary. 
4.11 Subgroup analysis 
Safety and immune 
response have been added 
to the subgroup analysis.  
For the purpose of 
reference 


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5 
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Little, R.C, et al. 2006. SAS for Mixed Model, Second Edition, Cary, NC: SAS 
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SAS Online Doc 9.1.3. http://support.sas.com/onlinedoc/913/docMainpage.jsp 
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Kincaid C. 2005. Guidelines for selecting the covariance structure in mixed model 
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Baer MR, George SL, Caligiuri MA, Sanford BL, Bothun SM, Mrózek K, et al. 
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Hellstrand K, Romero A, Brune M. Immunotherapy with Histamine Dihydrochloride 
and Interleukin-2 in Acute Myeloid Leukaemia. European Haematology, 
2008;2(1):71-4 
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Farag SS, George SL, Lee EJ, Baer M, Dodge RK, Becknell B, et al. Postremission 
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Cancer and Leukemia Group B study 9420. Clin Cancer Res. 2002;8(9):2812-9. 
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Portal Site of Official Statics of Japan (e-Stat): Statistics Bureau, Ministry of Internal 
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http://www.e-stat.go.jp/SG1/estat/eStatTopPortal.do 
9 
Kurosawa S. Comparison of post-remission strategies in elderly patients with acute 
myeloid leukemia in first complete remission, Rinsho Ketsueki. 2011;52(8):645-52. 
10 Klaus Rostgaard Methods for stratification of person-time and events- a prerequisite 
for Poisson regression and SIR estimation: Epidemiologic Perspectives & Innovations 
2008, 5:7 
11 Leslie E. Daly Confidence limits Made easy: Interval Estimation using a Substitution: 
American Journal of Epidemiology, Vol 147, No 8 
12 EORTC QLQ C30 version 3.0 
13  EORTC QLQ C30 Scoring Manual Third edition, 2001 
14  ICH Harmonized Guideline, THE CLINICAL EVALUATION OF QT/QTC INTERVAL 
PROLONGATION AND PROARRHYTHMIC POTENTIAL FOR NON-ANTIARRHYTHMIC 
DRUGS (E14), 2005-05-12