Clinical trial NCT02653976
Conditions: Peripheral T-Cell Lymphoma
Sponsor: Solasia Pharma K.K.
Start date: 2016-03-25; Completion date: 2021-06-17
Enrollment: 67 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is a phase 2 multinational, multicenter, single-arm, open-label, non-randomized study to evaluate the efficacy and safety of SP-02L monotherapy in relapsed or refractory patients with peripheral T-cell lymphoma.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: SP-02L (darinaparsin for injection)
Intervention descriptions: intervention 1: Darinaparsin 300 mg/m2 once daily for 5 consecutive days every 21 days

Protocol documents:
Prot_000.pdf: 
Product: SP-02L 
Protocol Number: SP-02L02 
Ver. 3.5: Date: 24 January 2020 
 
CONFIDENTIAL 
 
Solasia Pharma K.K. 
 
 
 
 
 
Asian Multinational Phase 2 Study of SP-02L (darinaparsin for injection)  
in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma 
PROTOCOL 
Protocol Number: SP-02L02 
 
 
 
 
Local Sponsor : 
<< XXXXXXXXXXX >> 
 
 
Development Sponsor : 
Solasia Pharma K.K. 
4F Sumitomo Fudosan Shiba-koen Tower,2-11-1, 
Shiba-koen, Minato-ku, Tokyo 105-0011, Japan 
 
 
 
Version : 
3.5 
Date of Issue : 
24 January 2020 
 
 
 
 
Confidentiality Notice 
This document contains confidential information of Solasia Pharma K.K. and the original 
licenser of this product. This document must not be disclosed to anyone other than the 
study staff (including investigator, sub-investigator, clinical research coordinator, study 
secretariat, investigational drug administrator) and members of the institutional review 
board without the prior written consent of Solasia Pharma K.K. The information in this 
document cannot be used for any purpose other than the evaluation or conduct of the 
clinical investigation without the prior written consent of Solasia Pharma K.K. 
 


Product: SP-02L 
Protocol Number: SP-02L02 
Ver. 3.5: Date: 24 January 2020 
 
CONFIDENTIAL 
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Solasia Pharma K.K. 
PROTOCOL SYNOPSIS 
Title 
Asian Multinational Phase 2 Study of SP-02L (darinaparsin for injection) in 
Patients with Relapsed or Refractory Peripheral T-cell Lymphoma  
Target Disease 
Relapsed or refractory peripheral T-cell lymphoma (PTCL) 
Study Phase 
2 
Objectives 
[Primary Objective] 
To evaluate the efficacy of SP-02L monotherapy in patients with relapsed or 
refractory PTCL 
[Secondary Objectives] 
 
To evaluate the safety of SP-02L monotherapy in patients with relapsed or 
refractory PTCL 
 
To assess the pharmacokinetic (PK) profile of SP-02L at multiple doses in a 
subgroup of subjects 
Study Design 
This study is a phase 2 multinational, multicenter, single-arm, open-label, 
non-randomized study conducted in East Asia countries/regions. Subjects will 
receive SP-02L at 300 mg/m2 once daily for 5 consecutive days followed by 
16 days of rest per cycle of 21 days (3 weeks). SP-02L will be administered for 
6 cycles to evaluate the efficacy and safety of SP-02L monotherapy by using 
various endpoints. If the subject wishes to continue investigational drug 
administration and the principal investigator judges that the continued 
administration of investigational drug is possible and necessary for the subject, 
the investigational drug administration can be continued beyond 6 cycles. 
Pharmacokinetics will be assessed in subjects enrolled in a part or all of the 
investigational sites in each of participating country or region at Cycle 1. 
Endpoints 
[Primary Endpoint] 
Tumor response (best overall response) according to the Revised Response 
Criteria for Malignant Lymphoma by an International Working Group to 
Standardize Response Criteria for Non-Hodgkin's Lymphomas in 2007 
[Secondary Endpoints] 
 
Progression-free survival (PFS), time to response (TTR), duration of 
response (DOR) and overall survival (OS) 
 
Occurrence of adverse events (AEs) 
 
Drug plasma concentration-time profile, PK parameters, and urinary 
excretion rates 
Planned number of 
subjects 
65 subjects 
The target number of subjects to be included in PK assessment is about 10 in 
each of participating country/region 


Product: SP-02L 
Protocol Number: SP-02L02 
Ver. 3.5: Date: 24 January 2020 
 
CONFIDENTIAL 
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Solasia Pharma K.K. 
Planned Study 
Duration 
December 2015 to December 2021 (planned) 
Eligibility Criteria 
[Inclusion criteria] 
(1) 
Patients with ethnic background of each participating country/region; 
(2) 
Patients aged ≥ 20 years of age at the date of obtaining informed consent; 
(3) 
Patients with histopathologically confirmed diagnosis of one of the following: 
・ Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS); 
・ Angioimmunoblastic T-cell Lymphoma (AITL); 
・ Anaplastic large cell lymphoma (ALCL), (ALK-positive/negative); 
The pathology specimens supporting the local diagnosis should be 
submitted for the central pathology review by the Pathological Review 
Committee. 
(4) 
Patients have a treatment history of at least one regimen with antitumor 
agents for the above diseases; 
(5) 
Patients have an enlarged lymph node or extranodal mass lesion that is 
measurable on computed tomography (CT); 
In this study, a measurable enlarged lymph node is defined as a lesion of 
> 1.5 cm in greatest transverse diameter regardless of short axis 
measurement or > 1.0 cm in short axis regardless of greatest transverse 
diameter, that is clearly measurable in 2 perpendicular dimensions. A 
measurable extranodal mass lesion is defined as a lesion of ≥ 1.0 cm in 
greatest transverse diameter (two times longer than the scan slice 
thickness). A nodular mass within the liver or spleen is defined as a 
space-occupying lesion of ≥ 1.0 cm in 2 perpendicular dimensions. 
(6) 
Patients with Eastern Cooperative Oncology Group Performance Status 
(ECOG-PS) of 0, 1, or 2; and 
(7) 
Patients with a life expectancy of at least 3 months (e.g. no acute 
exacerbation of their primary disease) as determined by the principal 
investigator or sub-investigator.  
[Exclusion Criteria] 
(1) 
Patient with inadequately maintained major organ functions as evidenced by 
the following laboratory test values taken at the screening visit. These 
laboratory test values should not be affected by blood transfusion or 
administration of hematopoietic growth factor agents, etc. Even though the 
patients who meet none of the following criteria, subject’s condition should 
not show an obvious tendency toward worsening as determined by the 
principal investigator or sub-investigator: 
・ Electrocardiogram (ECG): Fridericia-corrected QT interval (QTcF) 
≥ 450 msec; 
・ Hemoglobin: < 8.0 g/dL; 
・ Neutrophil count: < 1,000/mm3; 


Product: SP-02L 
Protocol Number: SP-02L02 
Ver. 3.5: Date: 24 January 2020 
 
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Solasia Pharma K.K. 
・ Platelet count: < 50,000/mm3; 
・ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): 
> 3 times ULN defined at the investigational site; or 
・ Creatinine: > 1.5 times ULN defined at the investigational site; 
(2) 
Patients with a positive result for either hepatitis C virus antibody (HCV 
antibody) or hepatitis B virus (HBV) surface antigen (HBs antigen) test 
during the screening period. Alternatively, the patients with a negative result 
for HBs antigen; however, with a positive result for either HBV surface 
antibody (HBs antibody) or HBV core antibody (HBc antibody), and with an 
HBV deoxyribonucleic acid (DNA) level (HBV-DNA level) ≥ the detection 
sensitivity of the assay; 
(3) 
Patients who are known to be positive for human immunodeficiency virus 
antibody (HIV antibody) or human T-cell leukemia virus type I antibody 
(HTLV-1 antibody); 
(4) 
Patients who are known or suspected metastasis or invasion to the central 
nervous system, or lymphoma lesions in the central nervous system; 
(5) 
Patients who have a concurrent active malignancy other than PTCL with the 
disease- or treatment-free period of < 5 years, excluding skin basal cell 
carcinoma, skin squamous cell carcinoma and carcinoma in situ of the 
cervix that are judged to have been cured; 
(6) 
Patients who have concurrent or a past history of central nervous system 
disease (e.g. seizure, dementia, Parkinson’s disease, Alzheimer’s disease), 
cerebrovascular disorder (e.g. transient ischemic attack, cerebral infarction, 
cerebral hemorrhage), or psychiatric disorder (e.g. schizophrenia, 
depression, addiction); 
(7) 
Patients who concurrently have any of the following conditions: 
・ Congenital long QT syndrome; 
・ Poorly controlled cardiac arrhythmia; 
・ Poorly controlled diabetes mellitus; 
・ Infections requiring systemic administration of antibiotic, antifungal or 
antiviral drugs; 
・ Acute hepatitis, chronic hepatitis, or liver cirrhosis; or 
・ Serious acute or chronic organ dysfunction (e.g. cardiac, hepatic, renal, 
or respiratory failure); 
(8) 
Patients who have known or suspected hypersensitivity to arsenic; 
(9) 
Patients who have used agents containing darinaparsin; 
(10) Patients who have received anticancer chemotherapy (including continuous 
use of oral administration or injection of corticosteroids equivalent to 
> 10 mg/day of prednisolone, as anticancer therapy) or anticancer 
immunotherapy (excluding antibody therapy) within 3 weeks before the day 
of subject enrollment; 


Product: SP-02L 
Protocol Number: SP-02L02 
Ver. 3.5: Date: 24 January 2020 
 
CONFIDENTIAL 
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Solasia Pharma K.K. 
(11) Patients who have received antibody therapy (including investigational 
drugs) within 12 weeks before the day of subject enrollment; 
(12) Patients who have received radiotherapy within 3 weeks before the day of 
subject enrollment;  
(13) Patients who have received autologous hematopoietic stem cell transplant 
within 12 weeks before the day of subject enrollment, or patients who have 
received allogeneic hematopoietic stem cell transplant;  
(14) Patients who underwent major surgery (e.g., surgery requiring systemic 
anesthesia, craniotomy, thoracotomy, or laparotomy) within 4 weeks before 
the day of subject enrollment; 
(15) Patients who are participating in other clinical trials or received any 
investigational drug or device within 4 weeks before the day of subject 
enrollment; 
(16) Patients who are unable to stay in the hospital for the period specified in the 
protocol; 
(17) Female patients who are breast-feeding, pregnancy or planned pregnancy; 
(18) Patients of reproductive potential who will not be able to use adequate 
contraceptive precautions during the treatment period and following 
3 months after the last dosing of investigational drug; in the judgment of the 
principal investigator or sub-investigator; or 
(19) Patients with considerable concern for compliance with the protocol, in the 
judgment of the principal investigator or sub-investigator. 
Dosage and 
dosing schedule of 
the investigational 
drug 
Subjects will receive SP-02L at 300 mg/m2 once daily for 5 consecutive days 
(Days 1-5) followed by 16 days of rest per cycle of 21 days (3 weeks). SP-02L will 
be administered for 6 cycles according to the protocol-specified criteria of 
postponement (skip) of administration, dose reduction and treatment 
discontinuation. If the subject wishes to continue investigational drug 
administration and the principal investigator judges that the continued 
administration of investigational drug is possible and necessary for the subject, 
the investigational drug administration can be continued beyond 6 cycles. 
Reconstituted and diluted SP-02L solution should be infused intravenously over 
1 hour (± 10 minutes) on each dosing day. Because the injection site 
abnormalities have been frequently reported in subjects who received SP-02L 
infusion via a peripheral line in the previous clinical studies, the investigational 
drug is recommended to be administered through the central vein. 


Product: SP-02L 
Protocol Number: SP-02L02 
Ver. 3.5: Date: 24 January 2020 
 
CONFIDENTIAL 
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Solasia Pharma K.K. 
Prohibited 
concomitant 
therapy 
Throughout the study (from the day of obtaining the informed consent to the end 
of follow-up period), none of the medications or treatments listed below should be 
proscribed for any reason:  
 
Anticancer chemotherapy or anticancer immunotherapy, other than the 
investigational drug; 
Continuous use of oral administration or injection of corticosteroids 
(equivalent to > 10 mg/day of prednisolone) is also prohibited. However, 
single or as-needed use for the treatment of fever or pretreatment for blood 
transfusion etc. is allowed. 
 
Radiotherapy; 
 
Hematopoietic stem cell transplants; 
 
Cellular immunotherapy (e.g., cancer vaccine therapy); 
 
Gene therapy; 
 
Major surgery (e.g., surgery with general anesthesia, 
craniotomy/thoracotomy/laparotomy); 
 
Any other investigational drugs, therapeutic drugs that are not approved by 
regulatory agency in each country or region (excluding drugs already 
approved for off-label use) and investigational device. 
Study Procedures 
See “Schedule of Study Procedures” 
Statistical 
Procedures 
Based on a central assessment at Efficacy and Safety Review Committee, the 
best overall responses for 6 cycles will be summarized to calculate the overall 
response rate (ORR) and 90% confidence interval (90% CI). Based on a local 
assessment at each investigational site, the best overall responses for 6 cycles 
and in the entire period will be summarized to calculate ORR and 90% CI. 
To assess the tumor response in each subject, the waterfall plot will be produced 
to show the rate of tumor shrinkage at best overall response. 
PFS, TTR, DOR and OS will be summarized overall and by histopathological 
subtype. PFS and OS will be analyzed by using Kaplan-Meier methods overall 
and by histopathological subtype. 
The occurrence of AEs will be summarized by system organ class and by 
preferred term according to the MedDRA, and by ethnic background and by 
severity. The occurrence of investigational-drug-related AEs, serious AEs or 
investigational-drug-related serious AEs will be also summarized in a similar way. 
In the PK analysis, drug concentration will be summarized overall and by ethnic 
background, and the graphs of mean drug concentration-time profiles will be 
provided. The PK parameters for each subject will be estimated using 
non-compartmental methods and summarized overall and by ethnic background. 
Urinary excretion rates will be calculated and summarized overall and by ethnic 
background. 
 


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Protocol Number: SP-02L02 
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Schedule of Study Procedures
 
Screening 
Period 
Treatment Period 
Follow-up 
Period 
Study  
Completion /  
Discontinuation 
Day 
−28 to −1 
1 
2 
3 
4 
5 
6 
8 
15 
22 to 42 
- 
IC 
 
22 
 
Informed Consent (IC) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Background 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Primary Disease 
X 
 
 
 
 
 
 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
X*1 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
X 
X*2 
 
 
 
 
 
 
 
 
 
 
Body Height 
X 
 
 
 
 
 
 
 
 
 
 
 
Body Weight 
X 
X*2 
 
 
 
 
 
 
 
 
 
 
Subject Enrollment 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Hospitalization 
 
C1 
C1 
C1 
C1 
C1 C1*3 
 
 
 
 
 
SP-02L Administration 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Time Window (day) - 
- 
- 
- 
- 
- 
- 
±2 
+6 
+7 
 
 
Physical Examination 
X 
X*2 
 
 
 
C1*4 
 
X 
X 
X 
 
 
Vital Sign and Arterial SaO2 
Measurement 
X 
X*2 
 
 
 
C1*4 
 
X 
X 
X 
 
 
ECG 
X 
X*5 
 
 
 
C1*5 
 
X 
 
X 
 
 
Laboratory Test 
X*6 
X*2 
 
 
 
C1*4 
 
X 
X 
X 
 
 
Con. Med. Reporting 
 X 
 
 
Adverse Event Reporting 
 
 X 
 
 
Assessment of Lymphoma 
Lesions 
X 
 
 
 
 
 
 
 
X*7 
X*7 
 
End of Study 
 
 
 
 
 
 
 
 
 
 
X*8 
The following procedures will be performed only at the investigational sites 
where a principal investigator’s agreement to perform these procedures is made prior to the study start 
Blood Sampling for Plasma PK 
 
C1*9 C1*9 C1*9 C1*9 C1*9 C1*9 C1*9 C1*9 
 
 
 
Urinary Collection for Urine PK 
 
C1*9 C1*9 
 
 
C1*9 C1*9 
 
 
 
 
 
C1: Only in Cycle 1 
*1: Disease status of concurrent disease is identified prior to the start of SP-02L dosing on Day 1 in Cycle 1 
*2: Prior to the start of SP-02L dosing 
*3: Subjects for PK assessment are hospitalized until the completion of blood/urine collection on Day 6 
*4: Within 60 minutes after the end of drip infusion. Physical Examination on Day 5 is given after the end of drip 
infusion. 
*5: Prior to SP-02L dosing and within 60 minutes after the end of drip infusion 
*6: Hepatitis virus test is performed in the screening period 
*7: On any day during the period from Day 15 to Day 21 in Cycle 3 and 6, and in every 3±1 cycles from Cycle 7. On 
any day during the period of Day 15 to Day 42 in the last cycle and prior to the start of subsequent treatment.  
*8: Following the day of study completion, survival surveillance will be continued for up to 2 years from the day of the 
1st dosing of SP-02L in Cycle 1.  
*9: See “Schedule for Blood and Urine Sample Collection for PK Assessment” (shown in the next page) 


Product: SP-02L 
Protocol Number: SP-02L02 
Ver. 3.5: Date: 24 January 2020 
 
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Solasia Pharma K.K. 
Schedule for Blood and Urine Sample Collection for PK Assessment
Day 
1 
2 
3 
4 
Time from the start of  
SP-02L infusion (hour) 
0 
1 
2 
4 
6 
8 
0 
0 
0 
Time from the end of  
SP-02L infusion (hour) 
- 
Just after 
the end of 
infusion 
1 
3 
5 
7 
- 
- 
- 
Time Window (minutes) 
Before 
starting 
infusion 
-60 
After the 
end of 
infusion 
+15 
±15 
±15 
±30 
±30 
Before 
starting 
infusion 
-60 
Before 
starting 
infusion 
-60 
Before 
starting 
infusion 
-60 
SP-02L Administration 
X 
 
 
 
 
X 
X 
X 
Blood Sampling for Plasma PK 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Collection for Urine PK 
X*1 
[0-4 hours] 
X*2 
[4-24 hours] 
 
 
Day 
5 
6 
8 
15 
Time from the start of  
SP-02L dosing (hour) 
0 
1 
2 
4 
6 
8 
(*3) 
(*3) 
- 
Time from the end of  
SP-02L infusion (hour) 
- 
Just after 
the end of 
infusion 
1 
3 
5 
7 
- 
- 
- 
Time Window (minutes) 
Before 
starting 
infusion 
-60 
After the 
end of 
infusion 
+15 
±15 
±15 
±30 
±30 
±60 
±60 
- 
SP-02L Administration 
X 
 
 
 
 
 
 
 
Blood Sampling for Plasma PK 
X 
X 
X 
X 
X 
X 
X 
X 
X*4 
Urine Collection for Urine PK 
X*1 
[0-4 hours] 
X*2 
[4-24 hours] 
 
*1: For 4 hours from the start of SP-02L infusion (until 3 hours from the end of infusion), on Day 1  
and Day 5  
*2: For 20 hours from 4 hours after the start of SP-02L infusion, on Day 1 and Day 5 
*3: At the same time of the start of SP-02L infusion on Day 5 
*4: Window: Day 15 - 21 
 
 


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LIST OF AVVREVIATION 
Abbreviation 
Term 
AITL 
Angioimmunoblastic T-cell Lymphoma  
ALCL 
Anaplastic Large Cell Lymphoma  
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BSA 
Body Surface Area 
CR 
Complete Response 
CRu 
Complete Response/unconfirmed 
CT 
Computed Tomography  
DOR 
Duration of Response  
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture  
FDG-PET 
Fluorodeoxyglucose-Positron Emission Tomography 
GCP 
Good Clinical Practice  
HBc antibody 
Hepatitis B Virus Core antibody 
HBs antibody 
Hepatitis B Virus Surface antibody 
HBs antigen 
Hepatitis B Virus Surface antigen  
HBV 
Hepatitis B Virus 
hCG 
human Chorionic Gonadotropin 
HCV antibody 
Hepatitis C Virus antibody  
HIV antibody 
Human Immunodeficiency Virus antibody 
HTLV-1 antibody 
Human T-cell Leukemia Virus type I antibody 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use  
IPI 
International Prognostic Index  
IUD 
Intra-uterine Device 
MedDRA 
Medical Dictionary for Regulatory Activities  


Product: SP-02L 
Protocol Number: SP-02L02 
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Abbreviation 
Term 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events  
ORR 
Overall Response Rate 
OS 
Overall Survival 
PD 
Progressive Disease 
PET 
Positron Emission Tomography  
PFS 
Progression-Free Survival  
PIT 
Prognostic Index for T-cell lymphoma 
PR 
Partial Response 
PS 
Performance Status  
PTCL 
Peripheral T-cell Lymphoma 
PTCL-NOS 
PTCL-not otherwise specified 
QTcF 
Fridericia corrected QT interval 
RD 
Relapsed Disease 
SD 
Stable Disease 
TTR 
Time to Response 
WHO 
World Health Organization 
 


Product: SP-02L 
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STUDY GLOSSARY 
Abbreviation/Acronym/Term 
Definition 
SP-02 
Drug Substance code of darinaparsin 
SP-02L 
Product code of darinaparsin for injection 
Day 1 
The first day of 5 consecutive days of investigational drug administration in 
each cycle; including the case that the planned dosing on the first day is 
skipped 
the first screening visit 
The day on which the subject signs the informed consent 
Screening period 
The period from the day of the first screening visit to the day before the first 
day of the investigational drug administration (Day 1 of Cycle 1) 
Treatment period 
The period from the first day of the investigational drug administration (Day 
1 of Cycle 1) to the day before the first examination, observation and 
investigation scheduled during the follow-up period 
End of follow-up period 
The day on which the last (latest) examination, observation and 
investigation scheduled during the follow-up period is performed 
Follow-up period 
The period from the day of the first examination, observation and 
investigation scheduled during the follow-up period to the end of follow-up 
period  
Study period 
The period consists of “screening period”, “treatment period” and “follow-up 
period” 
Measurable lymphoma 
lesions 
 
A measurable enlarged lymph node is defined as a lesion of 
> 1.5 cm in greatest transverse diameter regardless of short axis 
measurement or > 1.0 cm in short axis regardless of greatest 
transverse diameter that is clearly measurable in 2 perpendicular 
dimensions. 
 
A measurable extranodal mass lesion is defined as a lesion of 
≥ 1.0 cm in greatest transverse diameter (two times longer than the 
scan slice thickness). 
 
A nodular mass within the liver or spleen is defined as a 
space-occupying lesion of ≥ 1.0 cm in 2 perpendicular dimensions. 
Tumor response 
“Complete Response (CR)” and “Partial Response (PR)” 
Overall Response Rate 
Proportion of subjects with “CR or PR” in the evaluable subject population 
Progression-Free Survival 
(PFS) 
Time from the first day of investigational drug administration (Day 1 of 
Cycle 1) to the date of "progressive disease" or "relapsed disease", or the 
date of "death", which occurs earlier 


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Abbreviation/Acronym/Term 
Definition 
Overall Survival (OS) 
Time from the first day of investigational drug administration (Day 1 of 
Cycle 1) to the date of "death" from any cause 
Time to Response (TTR) 
Time from the first day of investigational drug administration (Day 1 of 
Cycle 1) to the first day of tumor response observed for patients who 
achieved a CR or PR 
Duration of Response 
(DOR) 
Time from the first day of tumor response observed for patients who 
achieved a CR or PR to the date of "progressive disease" or "relapsed 
disease", or the date of "death" which occurs earlier 
Baseline 
Results at the last time point of examination, observation and investigation 
before the start of the first administration of investigational drug in Cycle 1 
 
 


Product: SP-02L 
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TABLE OF CONTENTS 
1. 
BACKGROUND AND RATIONALE ............................................................................... 1 
1.1. 
Target Disease ......................................................................................................... 1 
1.2. 
Investigational Drug ................................................................................................. 1 
1.3. 
Study Rationale ....................................................................................................... 4 
1.4. 
Hypothesis ............................................................................................................... 5 
2. 
STUDY PLAN ................................................................................................................. 6 
2.1. 
Target Disease ......................................................................................................... 6 
2.2. 
Study Phase............................................................................................................. 6 
2.3. 
Objectives ................................................................................................................ 6 
2.4. 
Study design ............................................................................................................ 6 
2.5. 
Endpoints ................................................................................................................. 7 
2.6. 
Sample Size ............................................................................................................. 7 
2.7. 
Estimated Study Duration ........................................................................................ 8 
2.8. 
Study Organization and Structure ........................................................................... 8 
3. 
SUBJECT ELIGIBILITY ................................................................................................. 9 
3.1. 
Inclusion Criteria ...................................................................................................... 9 
3.2. 
Exclusion Criteria ..................................................................................................... 9 
4. 
MANAGEMENT OF SUBJECTS ................................................................................. 12 
4.1. 
Informed Consent .................................................................................................. 12 
4.2. 
Safety Considerations for Subjects ....................................................................... 12 
4.3. 
Assignment of Subject Number ............................................................................. 13 
4.4. 
Completion or Withdrawal from Study in Individual Subject ................................. 14 
4.5. 
Replacement of Subject ........................................................................................ 15 
4.6. 
Study Suspension or Termination .......................................................................... 16 
5. 
TREATMENT PROCEDURES ..................................................................................... 17 
5.1. 
Packaging, Formulation and Storage of Investigational Product .......................... 17 
5.2. 
Preparation of Investigational Drug ....................................................................... 17 
5.3. 
Drug Dosage .......................................................................................................... 17 
5.4. 
Skip of Administration, Dose Reduction and Study Discontinuation ..................... 19 
5.5. 
Concomitant Therapy ............................................................................................ 21 
6. 
STUDY PROCEDURES ............................................................................................... 22 
6.1. 
Subject Background ............................................................................................... 22 
6.2. 
Medical History of Primary Disease ...................................................................... 22 
6.3. 
Lymphoid Tissue Specimen Submission ............................................................... 23 
6.4. 
Performance Status ............................................................................................... 23 
6.5. 
Medical History ...................................................................................................... 23 
6.6. 
Pregnancy Status .................................................................................................. 23 
6.7. 
Height and Weight Measurement .......................................................................... 24 


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6.8. 
Physical Examination............................................................................................. 24 
6.9. 
Vital Sign and Arterial Oxygen Saturation Measurement ...................................... 25 
6.10. Electrocardiogram (ECG) ...................................................................................... 25 
6.11. Laboratory Tests .................................................................................................... 26 
6.12. Concomitant Medication/Procedures .................................................................... 27 
6.13. Adverse Events ...................................................................................................... 27 
6.14. Lymphoma Lesions Assessment ........................................................................... 27 
6.15. Survival Surveillance ............................................................................................. 30 
6.16. Pharmacokinetics .................................................................................................. 30 
6.17. Reference: Volume of Blood Sample Collection ................................................... 33 
7. 
SAFETY DATA COLLECTION AND REPORTING ..................................................... 34 
7.1. 
Definitions .............................................................................................................. 34 
7.2. 
Procedures for Adverse Events Reporting ............................................................ 35 
7.3. 
Follow-up Observation of Adverse Events ............................................................ 35 
7.4. 
Reporting of Serious Adverse Events .................................................................... 36 
8. 
DATA COLLECTION AND MANAGEMENT ................................................................ 37 
8.1. 
Data Entry to Electronic Case Report Form (eCRF) ............................................. 37 
8.2. 
Correction or Change to Data in eCRF ................................................................. 37 
8.3. 
Data in eCRF as Source Data ............................................................................... 37 
8.4. 
Deviations from the Protocol ................................................................................. 38 
8.5. 
Committees and Coordinating Investigators ......................................................... 38 
9. 
STATISTICAL CONSIDERATIONS ............................................................................. 40 
9.1. 
Subsets .................................................................................................................. 40 
9.2. 
Sample Size Considerations ................................................................................. 40 
9.3. 
Interim Analysis ...................................................................................................... 40 
9.4. 
Planned Methods of Analysis ................................................................................ 41 
10. STUDY ADMINISTRATION AND ETHICAL CONSIDERATIONS .............................. 43 
10.1. General Ethical Requirements ............................................................................... 43 
10.2. Protocol Management............................................................................................ 43 
10.3. Quality Control and Quality Assurance .................................................................. 43 
10.4. Retention of Study Records ................................................................................... 44 
10.5. Subject Confidentiality ........................................................................................... 44 
10.6. Health Damage Compensation ............................................................................. 44 
10.7. Publication ............................................................................................................. 45 
11. REFERENCES ............................................................................................................. 46 
 
Appendix 1: ECOG Performance Status Scale 
Appendix 2: Pharmacy Guide 
Appendix 3: List of Development Sponsor, Medical Experts, Organization, and 
Institutions/CROs Related to Entire Study 


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1. 
BACKGROUND AND RATIONALE 
1.1. Target Disease 
The peripheral T-cell lymphoma (PTCL) is a type of non-Hodgkin lymphomas, which is 
categorized into a heterogeneous group of mature T-cell and NK-cell neoplasms. It is 
categorized as aggressive lymphoma that progresses on a monthly basis from the 
perspectives of malignancy and activity/aggressiveness. In Asia, Mature T-cell and NK-cell 
neoplasms account for approximately 15% to 20% of all types of lymphoid neoplasm. The 
most common PTCL is classified as PTCL-not otherwise specified (PTCL-NOS) and 
accounts for about 30% of T-cell lymphomas. No clear evidence exists for the initial 
treatment of T-cell lymphomas; anthracycline-containing combination chemotherapy include 
CHOP (combination chemotherapy regimen of cyclophosphamide, doxorubicin, vincristine 
and prednisolone) are commonly provided as regular medical care but are not considered to 
achieve sufficient treatment results. Moreover, no salvage therapy for patients with relapsed 
or refractory is established as the standard treatment, resulting in a poor prognosis. 
Therefore, the development of novel therapeutic agents with favorable tolerability and have 
different mechanisms of action from the existing antineoplastic agents is required so that 
they can be contained in a new combination chemotherapy that is aimed at improvement of 
treatment results.  
1.2. Investigational Drug 
See Investigator’s Brochure (IB) for the detailed information on this investigational drug 
(SP-02L). 
1.2.1. 
Origins and History of Discovery and Development 
Darinaparsin (International Nonproprietary Name), the active ingredient of the 
investigational drug (Product code: SP-02L) (darinaparsin for injection), is an organic 
arsenic compound with antitumor activity. The development program of this product was 
started by ZIOPHARM Oncology, Inc. in the US (ZIOPHARM). Solasia Pharma K.K. 
(Solasia) has acquired a worldwide license to develop and commercialize darinaparsin from 
ZIOPHARM and has been conducting its clinical development with the target indication of 
PTCL.  
Darinaparsin is the lead compound in a series of organic arsenics derivatives and this 
structure is one of the intermediate metabolites of the arsenic detoxification pathway in the 
body. Its place in the natural metabolic pathway is expected to result in lower toxicity and 
therefore a much wider therapeutic window.  
1.2.2. 
Nonclinical Overview 
The results of the previous nonclinical pharmacology studies indicated that darinaparsin had 
antitumor activity against hematologic cancers, and in vitro cell line screen suggests that 
this compound has cytotoxic activity against solid tumors as well. The mechanisms of action 
of darinaparsin include disruption of mitochondrial functions, increase in reactive oxygen 


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species (ROS), and effects on signal transduction. Darinaparsin induces cell cycle arrest 
and apoptosis and has potent anti-angiogenic activity. 
In the preceding nonclinical studies, no finding that interfere with clinical use of darinaparsin 
have been extracted in the preceding nonclinical studies.  
1.2.3. 
Clinical Overview 
Six clinical studies have been conducted by ZIOPHARM in subjects with various 
hematologic malignancies, solid tumors, multiple myeloma and hepatocellular carcinoma, 
respectively. Two clinical studies have been conducted by Solasia in subjects with PTCL. 
Overview of these eight studies is shown in Table 1. 
Table 1: Overview of Past Clinical Studies 
Protocol No. * 
Cancer Type / Country 
Phase 
Dosage and dosing schedule 
No. of 
Treated 
subjects 
SGL1001: 
Hematologic malignancies / US 
1 
78-214 mg/m2/day for 5 consecutive days 
followed by 23 days rest (1 cycle: 28 days)  
11 
SGL1002: 
Solid tumors / US 
1 
78-588 mg/m2/day for 5 consecutive days 
followed by 23 days rest (1 cycle: 28 days)  
40 
SGL2001: 
Multiple myeloma / US, Canada 
1 
109-420 mg/m2/day for 5 consecutive days 
followed by 23 days rest (1 cycle: 28 days) 
17 
 
2 
300 mg/m2/day for 5 consecutive days 
followed by 23 days rest (1 cycle: 28 days) 
14 
SGL2001b: 
Multiple myeloma / US 
2 
420 mg/m2/day twice weekly for 3 weeks 
followed by 1 week rest (1 cycle: 28 days) 
17 
SGL2003: 
Hematologic malignancies / US, India 
2 
300 mg/m2/day for 5 consecutive days 
followed by 23 days rest (1 cycle: 28 days) 
50 
SGL2005: 
Hepatocellular carcinoma / US 
2 
420 mg/m2/day twice weekly for 3 weeks 
followed by 1 week rest (1 cycle: 28 days) 
15 
SP-02L01 : 
PTCL / Japan 
1 
200 or 300 mg/m2/day for 5 consecutive 
days followed by 16 or 23 days rest  
(1 cycle: 21 or 28 days) 
17 
SP-02L03 
PTCL / Korea 
1 
300 mg/m2/day for 5 consecutive days 
followed by 16 or 23 days rest  
(1 cycle: 21 or 28 days) 
6 
* 
Study numbers starting from “SGL” indicate studies conducted by ZIOPHARM Oncology, Inc.  
Study numbers starting from “SP-02L” indicate studies conducted by Solasia Pharma K.K. 


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1.2.4. 
Known and Potential Risks 
A total of 164 subjects received the investigational drug in 6 clinical studies conducted by 
ZIOPHARM. The integrated analysis includes all safety data collected and in the clinical 
data base as of March 31, 2012. Adverse events (AEs) occurring ≥ 5% of subjects across all 
studies that were reported by the investigator as being at least possibly related to 
investigational drug include nausea (20%), fatigue (18%), dizziness (9%), anemia (8%), 
vomiting (8%), headache (8%), confusional state (6%), diarrhea (5%), anorexia (5%), 
hypomagnesemia (5%), hyperglycemia (5%), and infusion site pain (5%). Of all Grade ≥ 3 
AEs that were considered possibly related to investigational drug, those occurring in 
≥ 2 subjects include fatigue (4%), hyperglycemia (4%), anemia (2%), febrile neutropenia 
(2%), neutropenia (2%), coordination abnormal (2%), confusional state (2%), infusion site 
pain (1%), hypoglycemia (1%), hypokalemia (1%), hypophosphatemia (1%), mental status 
changes (1%), and hypoxia (1%).  
In two phase 1 studies conducted by Solasia Pharma K.K. respectively in Japan and Korea 
in subjects with PTCL (Study SP-02L01 and SP-02L03), 23 subjects received the 
investigational drug. A integrated analysis of these two clinical studies indicated that 
investigational-drug-related AEs, occurring in ≥ 2 subjects, included constipation (17%), 
nausea (17%), malaise (17%), pyrexia (17%), alanine aminotransferase increased (17%), 
aspartate aminotransferase increased (17%), activated partial thromboplastin time 
prolonged (17%), decreased appetite (13%), somnolence (13%), platelet count decreased 
(13%), herpes zoster (9%), lymphopenia (9%), hallucination (9%), white blood cell count 
decreased (9%), neutrophil count decreased (9%), C-reactive protein increased (9%), and 
blood alkaline phosphatase increased (9%). Grade ≥ 3 investigational-drug-related AEs 
occurred in 4 of 23 subjects (17%), and included neutrophil count decreased (9%, 
2 subjects), platelet count decreased (9%, 2 subjects), diffuse large B-cell lymphoma (4%, 
1 subject), anaemia (4%, 1 subject), febrile neutropenia (4%, 1 subject), lymphopenia (4%, 
1 subject), nausea (4%, 1 subject), hepatic function abnormal (4%, 1 subject), lymphocyte 
count decreased (4%, 1 subject), white blood cell count decreased (4%, 1 subject), and 
activated partial thromboplastin time prolonged (4%, 1 subject).  
An extensive electrocardiogram (ECG) assessment in two clinical studies conducted 
respectively 
in 
Japan 
and 
Korea 
demonstrated 
that 
there 
was 
no 
drug-concentration-dependent 
nor 
treatment-duration-dependent 
change 
in 
Fridericia-corrected QT interval (QTcF) and there was no significant relationship between 
the plasma drug (arsenic) concentration of darinaparsin and a change in QTcF interval from 
time-matched baseline.  


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1.3. Study Rationale 
1.3.1. 
Target Disease 
In the phase 2 study (Study SGL2003) conducted by ZIOPHARM Oncology, Inc. in subjects 
with advanced hematologic malignancies who had failed at least 1 therapy and required 
treatment, darinaparsin was administered at 300 mg/m2 once daily for 5 consecutive days 
followed by 23 days rest (1 cycle: 28 days) for up to 6 cycles or until unacceptable toxicity or 
disease progression occurs. 
Out of a total of 50 subjects treated with the investigational drug, 29 were diagnosed with 
lymphomas (22 non-Hodgkin’s, 7 Hodgkin’s), 7 with acute myelogenous leukemia (AML), 
5 with chronic myelogenous leukemia (CML), 5 with myelodysplastic syndromes (MDS), 
2 with acute promyelocytic leukemia (APL), 1 with acute lymphoblastic leukemia (ALL), and 
1 with chronic myelomonocytic leukemia (CMML). There were 7 subjects with peripheral 
T-cell lymphoma (PTCL) and 5 of them were judged evaluable. The tumor responses (best 
overall response) in the evaluable subjects with PTCL resulted in complete response (CR) in 
1 subject and complete response/unconfirmed (CRu) in 1 subject. 
Since the above phase 2 study (Study SGL2003) confirmed that the investigational drug 
had favorable tolerability as well as potential antitumor activity against relapsed or refractory 
PTCL, Solasia Pharma K.K. conducted phase 1 studies (Study SP-02L01 and SP-02L03) in 
Japan and Korea, respectively, in subjects with relapsed or refractory PTCL. 
In phase 1 studies (Study SP-02L01 and SP-02L03) conducted in Japan and Korea, 
respectively, 200 or 300 mg/m2 of the investigational drug was administered once daily for 
5 consecutive days followed by 23 days rest (4-week cycle) or 16 days rest (3-week cycle). 
A total of 23 subjects, including 17 Japanese subjects in Japan phase I study (Study 
SP-02L01) and 6 Korean subjects in Korea phase 1 study (Study SP-02L03), received the 
investigational drug.  
One subject who received 300 mg/m2 of the investigational drug once daily for 
5 consecutive days followed by 16 days rest (3-week cycle) in Japan phase 1 study (Study 
SP-02L01) had a report of hepatic function disorder (Grade 3) which was determined as a 
Dose-Limiting Toxicity (DLT). The maximum tolerated dose (MTD) was not identified in 
either of these studies. The integrated analysis was conducted for the efficacies (tumor 
responses) of the investigational drug in 14 subjects who completed at least 2 cycles and 
had a tumor response assessment. The best overall response in the efficacy analysis set 
were complete response (CR) in 1 subject, partial response (PR) in 3 subjects, stable 
disease (SD) in 6 subjects and progressive disease (PD) in 4 subjects. Five of 6 subjects 
with stable disease showed tumor shrinkage to some extent.  
As described above, based on the previous clinical studies, no serious concern regarding 
safety of SP-02L was indicated, and preliminary tumor responses in patients with PTCL 
were confirmed, suggesting that the clinical development of SP-02L is positively significant 
for the treatment of this disease. 


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1.3.2. 
Study Design, Investigational Drug Dosage and Dosing Schedule 
This is a multinational multi-center study, and East Asian countries and region where there 
is no significant difference in disease incidence and treatment algorisms of malignant 
lymphoma and also in clinical trial implementation environment has been established. The 
comparison among pharmacokinetics (PK) profiles of investigational drug in Japanese and 
Korean subjects in phase 1 studies in Japan and Korea (Study SP-02L01 and SP-02L03) 
and Caucasian subjects in phase 1 study for solid tumors in the US (Study SGL1002) 
showed that the mean plasma concentration-time profiles were overlapping and systemic 
arsenic exposures were visually similar in Japanese, Korean, and Caucasian subjects at the 
doses studied. No statistically significant differences were found although only such a small 
number of subjects were evaluated in these studies. All the available data indicates there is 
no apparent ethnic difference in PK profiles in Japanese, Korean, and Caucasian subjects 
at the doses studied. 
An appropriate control arm (placebo or active comparator) cannot be set for this study 
because PTCL is categorized as aggressive lymphoma, any salvage therapy has not been 
established as the standard treatment for the relapsed or refractory cases, and patients are 
usually treated with multidrug combination chemotherapy. In addition, Revised Response 
Criteria for Malignant Lymphoma by an International Working Group to Standardize 
Response Criteria for Non-Hodgkin's Lymphomas in 2007 is used for the assessment of 
tumor response in this study, and the assessment with this response criteria using objective 
indicators enables less biased evaluation. Moreover, the central assessment at the Efficacy 
and Safety Review Committee will determine the tumor response that is the primary 
endpoint of this clinical trial. 
Therefore, the global, multi-center, single-arm, open-label, non-randomized design was 
considered appropriate for this clinical trial.  
As for the dosage and dosing schedule of investigational drug in this clinical trial, 
“300 mg/m2 once daily for 5 consecutive days followed by 16 days (3-week cycle) rest,” at 
which the tolerability and preliminary tumor response were confirmed in phase 1 studies in 
Japan and Korea (Study SP-02L01 SP-02L03) for relapsed or refractory PTCL, was 
selected. 
1.4. Hypothesis 
The study is expected to confirm the efficacy of SP-02L in subjects with PTCL, with the 
expected overall response rate (ORR) of 25% and the 10% threshold. 


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2. 
STUDY PLAN 
2.1. Target Disease 
Relapsed or refractory peripheral T-cell lymphoma (PTCL)  
2.2. Study Phase 
Phase 2 
2.3. Objectives 
2.3.1. 
Primary Objective 
To evaluate the efficacy of SP-02L monotherapy in patients with relapsed or refractory 
PTCL.  
2.3.2. 
Secondary Objectives 
 
To evaluate the safety of SP-02L monotherapy in patients with relapsed or refractory 
PTCL. 
 
To assess the pharmacokinetics (PK) profile of SP-02L at multiple doses in a subgroup 
of subjects [see Section 2.6]. 
2.4. Study design 
This study is a phase 2 multinational, multicenter, single-arm, open-label, non-randomized 
study conducted in East Asia countries/regions. Subjects will receive SP-02L at 300 mg/m2 
once daily for 5 consecutive days followed by 16 days of rest per cycle of 21 days (3 weeks). 
SP-02L will be administered for 6 cycles to evaluate the efficacy and safety of SP-02L 
monotherapy by using various endpoints. If the subject wishes to continue investigational 
drug administration and the principal investigator judges that the continued administration of 
investigational drug is possible and necessary for the subject, the investigational drug 
administration can be continued beyond 6 cycles. 
Pharmacokinetics will be assessed in subjects enrolled in part or all of the investigational 
sites in each of participating country or region at Cycle 1.  
Study design is shown in Figure 1.  
 
 
Figure 1: Study Design Schema 
Cycle 1 - 6 
300 mg/m2/day intravenously for 
5 consecutive days 
followed by 16 days rest 
(21-day cycle)  
Informed consent 
Enrollment 
Screening 
Survival surveillance 
Treatment 
continuation 
from Cycle 7 
Follow-up 
observation 


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2.5. Endpoints 
2.5.1. 
Primary Endpoint 
The primary endpoint is tumor response (best overall response) according to the Revised 
Response Criteria for Malignant Lymphoma by an International Working Group to 
Standardize Response Criteria for Non-Hodgkin's Lymphomas in 2007. 
The tumor response for 6 cycles that is confirmed by a central assessment at the Efficacy 
and Safety Review Committee is determined as the primary evaluation result, and that is 
confirmed by a local assessment at each investigational site is determined as the secondary 
evaluation result.  
2.5.2. 
Secondary Endpoints 
Secondary endpoints of this study are as follows. “Response” is defined as “complete 
response (CR)” or “partial response (PR)”.  
 
Progression-Free Survival (PFS） 
Defined as the time from the first day of investigational drug administration (Day 1 of 
Cycle 1) to the date of "progressive disease (PD)" or "relapsed disease (RD)", or the 
date of "death", which occurs earlier 
 
Time To Response (TTR) 
Defined as the time from the first day of investigational drug administration (Day 1 of 
Cycle 1) to the first day of tumor response observed for patients who achieved a CR or 
PR  
 
Duration of Response (DOR) 
Defined as the time from the first day of tumor response observed for patients who 
achieved a CR or PR to the date of PD or RD, or the date of "death", which occurs 
earlier 
 
Overall Survival (OS) 
Defined as the time from the first day of investigational drug administration (Day 1 of 
Cycle 1) to the date of "death" from any cause  
 
Occurrence of adverse events (AEs) 
 
Drug plasma concentration-time profile, PK parameters, and urinary excretion rates 
2.6. Sample Size  
The target number of subjects to be enrolled in this clinical trial is 65. 
PK assessments will be performed only at the investigational sites only at the investigational 
sites where a principal investigator’s agreement to perform these procedures is made prior 
to the study start, and in approximately 10 subjects in each of participating country/region.  


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2.7. Estimated Study Duration 
2.7.1. 
Study Duration for Individual Subject 
The period from the first screening visit at which the subject signs the informed consent to 
the day before the first day of the investigational drug administration (Day 1 of Cycle 1) is 
defined as a “screening period”. The period from the first day of the investigational drug 
administration (Day 1 of Cycle 1) to the day before the first examination, observation and 
investigation scheduled during the follow-up period is defined as a “treatment period”. The 
day on which the last (latest) examination, observation and investigation scheduled during 
the follow-up period is performed is defined as “the end of follow-up period”. The period from 
the day of the first examination, observation and investigation scheduled during the 
follow-up period to the end of follow-up period is defined as a “follow-up period”. 
The study period consists of “a maximum of 28 days of the screening period”, “21 days of 
the treatment period per cycle” and “21 days of the follow-up period, in general case”. The 
duration of this study is estimated to be a total of 175 days; 25 weeks; approximately 
6 months, when the subject is treated for 6 cycles. Additionally, the survival surveillance will 
be continued for up to 2 years from the first day of the investigational drug administration 
(Day 1 of Cycle 1). 
2.7.2. 
Entire Study Duration 
As from December 2015, the study will be initiated at each investigational site as the 
country- or region-specific regulatory requirements are satisfied in each country/region and 
each investigational site completes all procedures required for study initiation at each site. 
The end of survival surveillance in the last subject is planned to be completed in December 
2021.  
2.8. Study Organization and Structure 
This is a global multi-center study planned to be conducted in Japan, Korea, Taiwan and 
Hong Kong. At least one medical institution in each of these countries/regions will 
participate in this study. 
A list of names and addresses of the Development Sponsor, medical experts, committees, 
coordinating investigators and the institutions/CROs related to the entire study is provided in 
Appendix 3.  
A list of names and addresses of the investigational sites in each country and region, names 
of departments, names of the principal investigators, names and addresses of the local 
sponsor (the Sponsor) and local CROs, and names and contacts of study monitors, is 
provided as a separate document for “Study Organization and Structure in Each Country 
and Region”.  


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3. 
SUBJECT ELIGIBILITY 
3.1. Inclusion Criteria 
To be eligible for the study participation, patients must fulfill all of the following criteria: 
(1)  
Patients with ethnic background of each participating country/region; 
(2)  
Patients aged ≥ 20 years of age at the date of obtaining the informed consent; 
(3)  
Patients with histopathologically confirmed diagnosis of one of the following: 
- 
PTCL- not otherwise specified (PTCL-NOS);  
- 
Angioimmunoblastic T-cell Lymphoma (AITL);  
- 
Anaplastic Large Cell Lymphoma (ALCL), anaplastic lymphoma kinase (ALK) 
positive/negative); 
The pathology specimens supporting the local diagnosis should be submitted for the 
central pathology review by the Pathological Review Committee [See Section 6.3]. 
(4)  
Patients have a treatment history of at least one regimen with antitumor agents for the 
above diseases; 
(5)  
Patients have an enlarged lymph node or extranodal mass lesion that is measurable 
on computed tomography (CT); 
In this study, a measurable enlarged lymph node is defined as a lesion of > 1.5 cm in 
greatest transverse diameter regardless of short axis measurement or > 1.0 cm in 
short axis regardless of greatest transverse diameter, that is clearly measurable in 
2 perpendicular dimensions. A measurable extranodal mass lesion is defined as a 
lesion of ≥ 1.0 cm in greatest transverse diameter (two times longer than the scan 
slice thickness). A nodular mass within the liver or spleen is defined as a 
space-occupying lesion of ≥ 1.0 cm in 2 perpendicular dimensions. 
(6)  
Patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 
of 0, 1, or 2 [See Appendix 1]; and 
(7)  
Patients with a life expectancy of at least 3 months (e.g. no acute exacerbation of their 
primary disease) as determined by the principal investigator or sub-investigator. 
3.2. Exclusion Criteria 
To secure the safety of subjects and to eliminate potential factors that may have an effect on 
the evaluation of the investigational drug, subjects who meet any of the following criteria are 
not eligible for the study. 
3.2.1. 
Laboratory Test Values 
(1)  Patient with inadequately maintained major organ functions as evidenced by the 
following laboratory test values taken at the screening visit. These laboratory test 
values should not be affected by blood transfusion or administration of hematopoietic 
growth factor agents, etc. Even though the patients who meet none of the following 


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criteria, subject’s condition should not show an obvious tendency toward worsening as 
determined by the principal investigator or sub-investigator: 
- 
Electrocardiogram (ECG): Fridericia-corrected QT interval (QTcF) ≥ 450 msec; 
- 
Hemoglobin: < 8.0 g/dL; 
- 
Neutrophil count: < 1,000/mm3; 
- 
Platelet count: < 50,000/mm3; 
- 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): 
> 3 times ULN defined at the investigational site; or 
- 
Creatinine: > 1.5 times ULN defined at the investigational site; 
(2)  
Patients with a positive result for either hepatitis C virus antibody (HCV antibody) or 
hepatitis B virus (HBV) surface antigen (HBs antigen) test during the screening period. 
Alternatively, the patients with a negative result for HBs antigen; however, with a 
positive result for either HBV surface antibody (HBs antibody) or HBV core antibody 
(HBc antibody), and with an HBV deoxyribonucleic acid (DNA) level (HBV-DNA level) 
≥ the detection sensitivity of the assay; 
(3)  
Patients who are known to be positive for human immunodeficiency virus antibody 
(HIV antibody) or human T-cell leukemia virus type I antibody (HTLV-1 antibody); 
3.2.2. 
Disease Related 
(4)  
Patients who are known or suspected metastasis or invasion to the central nervous 
system, or lymphoma lesions in the central nervous system; 
(5)  
Patients who have a concurrent active malignancy other than PTCL with the disease- 
or treatment-free period of < 5 years, excluding skin basal cell carcinoma, skin 
squamous cell carcinoma and carcinoma in situ of the cervix that are judged to have 
been cured; 
(6)  
Patients who have concurrent or a past history of central nervous system disease (e.g. 
seizure, dementia, Parkinson’s disease, Alzheimer’s disease), cerebrovascular 
disorder (e.g. transient ischemic attack, cerebral infarction, cerebral hemorrhage), or 
psychiatric disorder (e.g. schizophrenia, depression, addiction); 
(7)  
Patients who concurrently have any of the following conditions: 
- 
Congenital long QT syndrome; 
- 
Poorly controlled cardiac arrhythmia; 
- 
Poorly controlled diabetes mellitus; 
- 
Infections requiring systemic administration of antibiotic, antifungal or antiviral 
drugs; 
- 
Acute hepatitis, chronic hepatitis, or liver cirrhosis; or 
- 
Serious acute or chronic organ dysfunction (e.g. cardiac, hepatic, renal, or 
respiratory failure); 
(8)  
Patients who have known or suspected hypersensitivity to arsenic;  


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3.2.3. 
Medications 
(9)  
Patients who have used agents containing darinaparsin; 
(10)  Patients who have received anticancer chemotherapy (including continuous use of 
oral administration or injection of corticosteroids equivalent to > 10 mg/day of 
prednisolone, as anticancer therapy) or anticancer immunotherapy (excluding 
antibody therapy) within 3 weeks before the day of subject enrollment; 
(11)  Patients who have received antibody therapy (including investigational drugs) within 
12 weeks before the day of subject enrollment; 
(12)  Patients who have received radiotherapy within 3 weeks before the day of subject 
enrollment; 
(13)  Patients who have received autologous hematopoietic stem cell transplant within 
12 weeks before the day of subject enrollment, or patients who have received 
allogeneic hematopoietic stem cell transplant; 
(14)  Patients who underwent major surgery (e.g., surgery requiring systemic anesthesia, 
craniotomy, thoracotomy, or laparotomy) within 4 weeks before the day of subject 
enrollment; 
(15)  Patients who are participating in other clinical trials or received any investigational 
drug or device within 4 weeks before the day of subject enrollment; 
3.2.4. 
General 
(16)  Patients who are unable to stay in the hospital for the period specified in the protocol 
[See Section 4.2.1];  
(17)  Female patients who are breast-feeding, pregnancy or planned pregnancy; 
(18)  Patients of reproductive potential who will not be able to use adequate contraceptive 
precautions during the treatment period and following 3 months after the last dosing of 
investigational drug; in the judgment of the principal investigator or sub-investigator; 
or 
(19)  Patients with considerable concern for compliance with the protocol, in the judgment 
of the principal investigator or sub-investigator. 


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4. 
MANAGEMENT OF SUBJECTS 
4.1. Informed Consent 
Before a subject’s participation in the clinical study, the principal investigator or 
sub-investigator is responsible for obtaining written informed consent from the subject 
himself/herself after adequate explanation of the study methods etc. to the subject and 
before any protocol-specified screening procedures in the subjects. The acquisition of 
informed consent should be documented in the subject’s medical records. 
If a potential subject is illiterate or visually impaired, the investigators must provide an 
impartial witness to read the informed consent form to the subject and give the subject an 
opportunity to ask questions. 
The informed consent form should be personally signed and dated by the subject, the 
principal investigator or sub-investigator, the witness (if applicable) and the person who 
conducted the informed consent discussion (if applicable). The original signed informed 
consent form should be retained in accordance with a rule of each investigational site, and a 
copy of the signed informed consent form should be provided to the subject. 
4.2. Safety Considerations for Subjects 
4.2.1. 
Hospitalization 
Subjects will be managed under hospitalization for at least 5 days from the first day of 
investigational drug administration (Day 1 to Day 5 of Cycle 1). Subjects for 
pharmacokinetic assessment [See Section 6.16] will be managed under hospitalization until 
the completion of blood and urine collection at Day 6 of Cycle 1 to ensure the completion of 
all time points of blood sampling for determination of drug plasma concentration and that of 
urine collection for determination of drug urine concentration. 
With no safety concern found in the results of protocol-specified examination, observation, 
the investigation performed during the hospitalization period, the principal investigators or 
sub-investigator will judge to discharges subjects.  
The principal investigator or sub-investigator (or designated staff) will enter the dates of 
hospitalization and discharge during the study period, into the electronic case report forms 
(eCRF) of this study.  
4.2.2. 
Methods of Contraception and Actions in Case of Pregnancy  
The principal investigator or sub-investigator (or designated staff) will instruct subjects to 
use validated methods of birth control throughout the study period and until three months 
following the last dosing of the investigational drug. In this study, abstinence or combined 
use of two or more of adequate contraception methods including but not limited to condom, 
intra-uterine device (IUD), and oral contraception will be recommended. 
The principal investigator or sub-investigator (or designated staff) must confirm negative 
pregnancy status of subjects at the screening visit and on Day 1 of each cycle (before the 


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start of investigational drug administration) [See Section 6.6].  
If the subject becomes pregnant during the study period, the subject must immediately be 
withdrawn from the study. 
If the pregnancy of subject or a subject’s partner is confirmed during the study period or 
within three months after the last administration of the investigational drug, the appropriate 
monitoring of subject should continue until conclusion of the pregnancy; e.g., progress 
during pregnancy, findings of intrapartum period and findings of neonate.  
The principal investigator or sub-investigator (or designated staff) must promptly notify the 
Sponsor, via study monitor, of the pregnancy of subject or a subject’s partner. The contact 
information of a study monitor is provided as a separate document for “Study Organization 
and Structure in Each Country and Region”. 
4.2.3. 
Instructions for Medical Imaging Tests at External Medical Institution  
In case that the investigational site will outsource the medical imaging tests including 
positron emission tomography (PET) to an external medical institution (hereinafter referred 
to as “collaborating medical institution”), the principal investigator will notify the Sponsor of 
the outsourcing of medical imaging tests to the collaborating medical institution. In addition, 
2-party contract between the investigational site and the collaborating medical institution, or 
3-party contract including the Sponsor should have been concluded for the outsourcing of 
medical imaging tests. Furthermore, the ordering procedures including how to share the 
information that the subject is participating in the clinical study, and the subject management 
procedures including how to get the information of AEs occurred at the collaborating 
medical institution, and also the image data submission procedures should be determined in 
advance.  
In the informed consent form, the principal investigator should describe that the medical 
imaging tests will be performed at the collaborating medical institution. The principal 
investigator or sub-investigator (or designated staff) will provide subject with the explanation 
about the study including the fact that the medical imaging tests will be performed at the 
collaborating institution, and then will obtain the informed consent from the study [See 
Section 4.1]. 
4.3. Assignment of Subject Number 
4.3.1. 
Notification of Informed Consent Acquisition and Assignment of Subject 
Number  
The principal investigator or sub-investigator (or designated staff) shall enter the date of 
consent (date written in the informed consent form) into the electronic data capture (EDC) 
system.  
Once the date of consent (date written in the informed consent form) is entered into the EDC 
system, a subject number will be assigned to an individual subject. In this study, subjects will 
be identified with subject numbers throughout the study period. The subject number will 


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consist of a total of 8-digits; the 3-digit protocol identifier (i.e., 2L2), followed by the 1-digit 
country/region number, the 2-digit site number, and the 2-digit subject number that will be 
assigned in sequential order at each investigational site. The subject number must remain 
unchanged throughout the study period; it must not be changed at the time of re-screening. 
4.3.2. 
Enrollment 
After the acquisition of the informed consent [See Section 4.1] and before the enrollment, 
the subjects will be screened for eligibility. Subjects who fail screening will be allowed to be 
re-screened. 
The principal investigator or sub-investigator (or designated staff) will enter the results of 
subject eligibility assessment [See Section 3] into the EDC system.  
Upon the subject’s eligibility is confirmed by the EDC system: when the subject’s eligibility 
data is accepted by EDC system, the procedures for subject registration will be completed. 
The date on which the EDC system has confirmed the subject’s eligibility shall be regarded 
as the date of subject’s enrollment (registration). 
4.4. Completion or Withdrawal from Study in Individual Subject 
The principal investigator or sub-investigator (or designated staff) will specify, if the enrolled 
subject has completed or been withdrawn from the study, date of the End of Study and the 
reason for withdrawal if applicable, and will enter them into the eCRF.  
4.4.1. 
Definition of Completion of Study and Day of End of Study 
The subjects who complete all of the examinations, observations and investigations 
scheduled during the follow-up period following the last treatment cycle, and also not meet 
any criteria for study withdrawal [See Section 4.4.2] will be determined as the subjects who 
completed study.  
< Day of End of Study > 
The day of “End of Study” will be at the end of follow-up period, except for the following 
cases: 
 
If a subject is withdrawn from the study before the first dosing of investigational drug, 
“the day on which the decision is made to withdraw the subject from the study” will be 
determined as the day of the End of Study. 
 
In a subject under the follow-up observation of ongoing AE [See Section 7.3], “the most 
recent (last) day on which an outcome of the AE is confirmed” will be determined as the 
day of the End of Study.  
 
If a subject is withdrawn from the study after the start of investigational drug 
administration and cannot continue any of the subsequent examination, observation 
and investigation; e.g., the subject is not willing to provide any own clinical data after the 
withdrawal of consent, or the pregnant subjects at a possible risk from protocol-specified 
examination, “the latest day on which the last examination, observation or investigation 
is performed” will be determined as the day of the End of Study. 


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 
If a subject dies during the study period, “the day of death” will be determined as the day 
of the End of Study. 
4.4.2. 
Study Withdrawal Criteria 
A subject who meets any of the following criteria may be withdrawn from the study: 
(1)  
Request to withdraw consent; 
(2)  
Ineligibility found after enrollment;  
(3)  
Pregnancy; 
(4)  
Impossibility of continuation of protocol-specified examination, observation and 
investigation due to subject’s own reason; e.g., difficulties in visiting the investigational 
site due to subject’s change of residence; 
(5)  
Subject’s serious non-compliance with the protocol; with the principal investigator’s or 
the Sponsor’s judgement for not continuing the study in the subject; 
(6)  
Serious violation of GCP or significant deviation from the protocol; with the principal 
investigator’s or the study sponsor’s judgement for not continuing the study in the 
subject;  
(7)  
Death of the subject; or 
(8)  
At the discretion of the principal investigator or the Sponsor.  
4.4.3. 
Procedures for Study Withdrawal 
In a subject who is withdrawn from the study before the first dosing of investigational drug, 
the subsequent examination, observation and investigation are not required to be 
performed.  
In a subject who is withdrawn from the study after the start of investigational drug 
administration and cannot continue any of the subsequent examination, observation and 
investigation; as cases such as the subject is not willing to provide any own clinical data 
after the withdrawal of consent or the subjects is pregnant at a possible risk from 
protocol-specified examination, the principal investigator or sub-investigator will take the 
best measures to stop the study in the subject, under the condition where the subject’s 
safety is ensured. In case of subjects have ongoing AEs, the best measures to follow the 
ongoing AEs should be carried out where possible.  
In a subject who is withdrawn from the study after the start of investigational drug 
administration; on the condition that the subject still has a willing to provide own clinical data, 
the subsequent examination, observation and investigation scheduled during the current 
cycle and the follow-up period should be completed. 
4.5. Replacement of Subject 
No replacement of subject will be taken in this study. Until the day on which the 
Development Sponsor confirms that the number of subjects who have received the 


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investigational drug for at least 1 cycle reaches the planned sample size, the notification of 
informed consent acquisition from a new patient and assignment of subject number to the 
subject will be accepted [See Section 4.3.1]. 
4.6. Study Suspension or Termination 
When the new information that seriously affects the continuation of the study is obtained, the 
Development Sponsor may decide to suspend or terminate the entire study, at all 
investigational sites. In case of study suspension or termination of the entire study, the 
Sponsor will notify it in writing with its reasons, to the principal investigators and 
investigational sites according to a country- or region-specific regulatory requirements. 
If the study is suspended or terminated, the principal investigators will provide the 
appropriate subsequent treatment to subjects.  


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5. 
TREATMENT PROCEDURES 
5.1. Packaging, Formulation and Storage of Investigational Product 
The investigational drug will be manufactured by a contract manufacturing organization that 
is appropriately selected and approved by the Development Sponsor. The Local Sponsor 
will distribute the investigational drugs to each investigational site through CRO or the 
investigational drug delivery service company. 
The investigational drug will be supplied as a sterile, white to off-white, lyophilized powder in 
glass vials containing 150 mg of darinaparsin per vial. Each vial and box will be labeled 
according to country- and region-specific regulations, and each box will have 10 vials of 
investigational drug. It should be stored under refrigeration at 2°C to 8°C (36°F to 46°F), 
except when being reconstituted and diluted for injection. 
5.2. Preparation of Investigational Drug 
Each vial contains 150 mg of darinaparsin. When completely reconstituted with 2.0 mL 
water for injection, the nominal concentration is 75 mg/mL. Within 1 hour of reconstitution, 
the required dose (mg) is drawn into at least one syringe and added to an infusion bag 
containing 250 mL of saline solution (Sodium Chloride Injection). 
In case that a lot number of investigational drug is multiple at the investigational site, the 
investigational drugs of the same lot number will be used in a subject throughout a cycle 
whenever possible; a subject will not receive the investigational drug of multiple lot numbers 
within a cycle.  
Details of investigational drug preparation are shown in Pharmacy Guide [See Appendix 2].  
5.3. Drug Dosage 
The principal investigator or sub-investigator (or designated staff) will enter the following 
information into the eCRF: 
 
Date of the investigational drug dosing, 
 
Start and stop time of dosing 
 
Dose (mg/m2) 
 
Administration route 
 
Lot number of investigational drug 
 
Completeness of administration; completed, interrupted or postponed (skipped) 
 
Actual volume of administration, if the administration is interrupted 
 
Reasons, if the administration is interrupted or postponed (skipped) 
 
Continuation to the next cycle or discontinuation at the end of current cycle 
 
Reason for discontinuation 


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5.3.1. 
Dosage and Administration Schedule 
Subjects will receive 300 mg/m2 of darinaparsin once daily for 5 consecutive days (Day 1 to 
Day 5) per 21-day cycle (3-week cycle) which consists of 5-day therapy followed by 16-day 
rest. The treatment will be given for 6 cycles according to the criteria in case of 
postponement (skip) of administration, dose reduction or discontinuation of treatment [See 
Section 5.4]. At the end of Cycle 6, if the subject wishes to continue investigational drug 
administration and the principal investigator judges that the continued administration of 
investigational drug is possible and necessary for the subject, the investigational drug 
administration can be continued beyond 6 cycles. Prior to the start of administration in 
Cycle 7, the principal investigator should notify the Sponsor via a study monitor of the 
continuation of treatment beyond 6 cycles. The contact of study monitor is provided as a 
separate document for “Study Organization and Structure in Each Country and Region”. 
The dose (mg) of the investigational drug given to each subject will be calculated by 
multiplying the subject’s body surface area (BSA, m2) by 300 (mg). The maximum dose will 
be 600 mg; a dose exceeding 600 mg per body must not be administered. 
The BSA will be calculated using DuBois’s formula shown below, based on the subject’s 
height (cm) and body weight (kg) measured during the screening period. 
S ＝ W0.425 × H0.725 × 0.007184 
S: Body surface area (m2) 
W: Weight (kg) 
H: Height (cm) 
 
If there are ±10% changes in the body weights measured on Day 1 of each cycle (before the 
start of investigational drug administration) from the weight measured in the screening 
period, BSA will be re-calculated to adjust the dose.  
The interval period between cycles from Cycle 1 to Cycle 6 (interval period between Day 21 
of a current cycle and Day 1 of the next cycle) will be allowed from -1 day up to +7 days for 
any reason. The interval period between cycles from Cycle 7 (including the interval period 
between Day 21 of Cycle 6 and Day 1 of Cycle 7) will be allowed from -1 day up to +14 days 
for any reason. 
5.3.2. 
Administration 
The investigational drug will be reconstituted and diluted according to the preparation 
procedures described in Section 5.2, and will be given intravenously over 1 hour 
(± 10 minutes) on each day of administration. After the infusion, a flushing with a sufficient 
amount of saline will be done to ensure all the drug remaining in the infusion route is infused 
fully to the subject. 
Since the injection site abnormalities have been frequently reported in subjects who 
received the investigational drug via a peripheral line in the previous clinical studies, the 


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administration of the investigational drug is recommended to be given through the central 
vein (e.g., via an implantable subcutaneous infusion port, a central venous catheter, a 
peripherally inserted central venous catheter). If any abnormal finding at the injection site is 
observed during the infusion via a peripheral line, the administration will be held at the 
discretion of the principal investigator or sub-investigator. Saline may be infused via a 
three-way stopcock. The IV infusion may be given from another peripheral vein or via a 
central venous line or port.  
The following matters should be noted when the investigational drug is administered: 
 
During the injection via a peripheral line, full care should be taken to avoid 
extravasation. If any extravasation is observed, the dose will be held immediately, 
medical procedures will be provided for it, and a change in the peripheral vein for 
IV infusion will be considered.  
 
No other drug for injection should be given concurrently via the same IV line. 
 
The investigational drug administration will be started at the same time as much as 
possible in subjects for pharmacokinetic assessment in Cycle 1 [See Section 6.16]. 
5.4. Skip of Administration, Dose Reduction and Study Discontinuation 
The medically important investigational-drug-related AEs that were reported in the previous 
clinical studies are including nervous system disorders (e.g. coordination abnormal) and 
psychiatric disorders (e.g. confusional state). Therefore, any finding of abnormalities or 
signs in nervous or psychiatric system will require to consider carefully for the skip 
(postponement) of administration, dose reduction or discontinuation of the investigational 
drug administration, regardless of the following criteria.  
5.4.1. 
Drug Administration Skip Criteria 
In case there is no alternative way on medical judgement of the principal investigator or 
sub-investigator, the investigational drug administration on the day may be skipped 
(postponed). In subject receiving the IV infusion, the infusion may be interrupted and 
stopped. If a Grade ≥ 3 AE related to the investigational drug is reported during the period 
from Day 1 to the completion of the investigational drug administration on Day 5, the IV 
infusion should be interrupted and stopped, and also the investigational drug administration 
subsequently planned in the current cycle should be skipped.  
However, in case of nausea, vomiting and diarrhea, only when the symptoms of these 
events are improved by symptomatic treatment; e.g., antiemetic drug for nausea and 
vomiting, and antidiarrheal drug for diarrhea, the investigational drug administration may be 
continued without a skip of administration.  
5.4.2. 
Dose Reduction Criteria 
If a Grade ≥ 3 AE related to the investigational drug is reported during the preceding cycle, 
the dose level of the investigational drug may be reduced to 200 mg/m2. However, the 
administration at 300 mg/m2 can be continued, at the discretion of the principal investigator, 
based on the consideration for the subject’s response to symptomatic treatment; e.g., 


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antiemetic drug for nausea and vomiting, and antidiarrheal drug for diarrhea, or supportive 
care; e.g., hematopoietic growth factor agents for hematological toxicity due to the 
investigational drug. 
Dose reduction will be allowed only one time for each subject, and the dose will not be 
returned to 300 mg/m2. 
5.4.3. 
Study Discontinuation Criteria 
If a subject meets any of the following criteria before the start of dosing in each cycle from 
Cycle 2, the subject will discontinue (not continue) the study without starting the 
investigational drug administration in the next cycle: 
(1)  
PD or RD at the tumor response assessment [See Section 6.14.2] 
(2)  
Clinical judgment of “symptomatic progression” by the principal investigator or 
sub-investigator; based on clinical symptoms or laboratory findings, etc., in case of no 
results of radiological assessment with PET/CT image data 
(3)  
Start of treatment with proscribed concomitant drugs or therapies [See Section 5.5.2] 
(4)  
A Grade 4 AE that is related to the investigational drug 
In case of the transient changes in laboratory test values without any clinically 
significant symptoms; e.g., the severity of changes in laboratory test values has 
recovered to “≤ Grade 2” within 7 days, the investigational drug administration will be 
continued at the discretion of the principal investigator  
(5)  
No improvement in the severity of an AE that is related to the investigational drug to 
“≤ Grade 1” or “Grade at pretreatment”  
The start of next cycle can be postponed for up to 3 weeks to allow the 
investigational-drug-related AE to be resolved. If the AE is not resolved to “≤ Grade 1” 
or “Grade at pretreatment” even though the start of next cycle is postponed for 
3 weeks, the subject will complete the study after the completion of the examinations, 
observations and investigations scheduled during the follow-up period. 
(6)  
No resolution or relapse of a similar investigational-drug-related AE at ≥ Grade 3 
despite a dose reduction of the investigational drug [See Section 5.4.2]  
However, the subject may continue receiving the investigational drug at a reduced 
dose at the discretion of the principal investigator, in case that the subject shows the 
response to the investigational drug; i.e., the tumor response in the subject is not 
assessed as PD or RD. 
(7)  
The principal investigator or sub-investigator decision not to continue investigational 
drug administration due to the occurrence of an investigational-drug-related AE, other 
than the events defined in (4), (5), and (6) above or other reasons. 


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5.5. Concomitant Therapy 
5.5.1. 
Permitted Concomitant Therapy and Limited Concomitant Therapy 
Throughout the study period, concomitant therapies including concomitant use of drugs 
required for medical reasons are permitted to use, except for the proscribed therapies 
described in Section 5.5.2. The use of antiemetic agents for nausea and/or vomiting, 
antidiarrheal agents for diarrhea, antimicrobial agents, antiviral agents, antifungal agents 
and gargles for opportunistic infection, and prophylactic antihyperuricemic agents for tumor 
lysis syndrome are also allowed. 
The use of drugs, which have been given to the subject before the start of investigational 
drug administration, for the treatment of chronic complication or as a symptomatic therapy 
for the primary disease will be continued during the study period at a consistent dosage and 
dosing schedule through the study period as far as possible, except when intolerable AEs 
due to these concomitant drugs occur. 
5.5.2. 
Proscribed Therapy 
Throughout the study, from the day of obtaining the informed consent to the end of follow-up 
period, none of the medications or treatments listed below should be proscribed for any 
reason. In any case a subject starts any of the medications or treatments for justifiable 
reasons, the subject will discontinue the study with the completion of examination, 
observation and investigation specified in the current cycle and the follow-up period: 
 
Anticancer chemotherapy other than the investigational drug, and anticancer 
immunotherapy 
Continuous oral administration or injection of corticosteroid: equivalent to more than 
10 mg/day of prednisolone, is also prohibited. However, single use or use as needed 
is allowed for the purpose including the treatment for fever or pretreatment for blood 
transfusion.  
 
Radiotherapy 
 
Hematopoietic stem cell transplants 
 
Cellular immunotherapy (e.g., cancer vaccine therapy) 
 
Gene therapy 
 
Major surgery; e.g., surgery with general anesthesia, craniotomy/thoracotomy 
/laparotomy)  
 
Any other investigational drugs, therapeutic drugs that are not approved by each 
country or region; excluding drugs which are already approved for off-label use, and 
investigational devices 


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6. 
STUDY PROCEDURES 
The principal investigator or sub-investigator (or designated staff) will enter the results of 
examination, observation and investigation specified in this Section 6, and also the dates 
and times for blood and urine collection, as needed, into the eCRF.  
The frequent performance of such invasive examinations and medical imaging tests; such 
as bone marrow biopsy and CT/PET imaging test, are considered medically and ethically 
unfavorable. Therefore, the bone marrow biopsy, CT and PET data that are obtained from 
routine medical practice before obtaining the informed consent from the subject may be 
allowed to be used as screening data of this study; only when these invasive examinations 
and medical imaging tests are performed within 28 days before subject enrollment. For the 
use of such data, a prior consent from the subject is required. However, PET data should be 
taken according to the study-specific procedures that is standardized by the Central Imaging 
Review institution of this study. 
The principal investigator or sub-investigator will be allowed to add the time points of 
examinations, observations and investigations as needed for the follow-up observation of 
AEs. 
6.1. Subject Background 
The following information regarding the subject background will be collected upon obtaining 
consent from the subject. 
 
Date of birth 
 
Sex 
 
Ethnic background: ethnic group, race 
6.2. Medical History of Primary Disease 
The following information regarding the medical history of primary disease will be collected 
on any day between Day -28 to Day -1 of the screening period. 
 
Histopathological diagnosis (histopathological subtype) of primary disease; made at 
the investigational site 
 
Date of diagnosis 
 
Clinical stage by the Ann Arbor Classification at a screening visit 
 
Prognostic risk group by International Prognostic Index (IPI) at a screening visit 
 
Prognostic risk group by Prognostic Index for T-cell lymphoma (PIT) at a screening 
visit 
 
Clinical symptoms caused by the primary disease (clinical symptoms associated with 
primary disease) 
 
Prior medication: name of regimen or drugs, periods of medication and responses to 
medication as needed 


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6.3. Lymphoid Tissue Specimen Submission 
Upon the subject’s enrollment, 15 unstained tissue specimens taken from the lymphoid 
tissue (lymph nodes, in principle); on which a local pathological diagnosis of primary disease 
is confirmed, will be submitted to the central laboratory of each country or region. Unstained 
tissue specimens will be prepared on coated glass slides; formalin-fixed paraffin-embedded 
≤5 μm-thick sections will be mounted on the coated glass slides. If prior biopsies were 
performed multiple times before subject enrollment, the principal investigator or a 
pathologist at each investigational site should submit the tissue specimens that are 
considered most valid basis for a local pathological diagnosis; either of the biopsy samples 
taken at an initial onset or at a relapse of disease are acceptable. According to the requests 
from the Pathological Review Committee, supplemental submission of unstained or stained 
tissue specimens may be requested. 
If less than 15 unstained tissue specimens can be submitted, as many unstained tissue 
specimens as possible and the previously-stained tissue specimens; that should include the 
specimen stained by hematoxylin and eosin staining, supporting the local pathological 
diagnosis should be submitted. The stained tissue specimens will be borrowed from the 
investigational site in accordance with each investigational site’s procedures.  
Details of the procedure for tissue specimen submission to the central laboratory of each 
country or region are specified in a separate document. At the central laboratory, the 
unstained tissue specimens will be stained at the direction of the Pathological Review 
Committee, and then all of tissue specimens will be submitted to the Pathological Review 
Committee.  
6.4. Performance Status 
Performance status will be determined according to ECOG performance status scale [See 
Appendix 1] on any day during the screening period (Day -28 to Day -1). 
6.5. Medical History 
The following information regarding the past and/or concurrent diseases including drug 
sensitivity and allergy will be collected on any day during the screening period (Day -28 to 
Day -1):  
 
Diagnosis or symptom, and date of diagnosis 
 
Drug sensitivity or allergy: if applicable, name of drug or allergen, severity 
Before the start of the first dosing of investigational drug on Day 1 of Cycle 1, whether or not 
the concurrent disease is ongoing at the start of investigational drug administration will be 
assessed. 
6.6. Pregnancy Status 
For subjects other than male and postmenopausal or surgically sterilized female subjects, a 
urine human chorionic gonadotropin (hCG) pregnancy test will be conducted on any day 


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during the screening period (between Day -28 to Day -1) and also before the start of 
investigational drug administration on Day 1 of each cycle. “Menopause” is defined as being 
at a state of absence of menstrual periods for at least 12 months, excluding the cases of 
absent menstruation due to a medical reason such as medication.  
Throughout the study period, the principal investigator or sub-investigator (or designated 
staff) should confirm that the subject or subject’s partner is not pregnant. 
6.7. Height and Weight Measurement 
Body height (cm) and weight (kg) will be measured on any day during the screening period 
(between Day -28 to Day -1). To determine the dose (mg) of the investigational drug, a body 
surface area (BSA: m2) will be calculated using the DuBois’s formula, based on the subject’s 
height and weight. [See Section 5.3.1] 
The subject’s body weight will be also measured before the start of investigational drug 
administration on Day 1 of each cycle. If the weight changes by ±10% compared to the 
weight measured at the screening visit, BSA will be recalculated using the DuBois’s formula 
to adjust the dose. [See Section 5.3.1] 
6.8. Physical Examination 
At each time point shown in Table 2, the principal investigator or sub-investigator will 
perform a physical examination. At the physical examination, careful assessment for 
neurological and mental status should be performed, especially for the following findings. 
 
Findings suggestive of cranial nerve abnormalities 
 
Findings suggestive of sensory abnormalities 
 
Findings suggestive of motor abnormalities  
 
Findings suggestive of coordination stance / gait abnormalities 
 
Findings suggestive of reflexes abnormalities 
 
Findings suggestive of mental status abnormalities  
Table 2: Time Points of Physical Examination in Cycle 
 
Time Point 
Time Window 
Screening Period 
Any day between Day -28 and -1 
 
Treatment Period 
Day 1; before the investigational 
drug administration  
Before the start of infusion  
Day 5; after the investigational drug 
administration: Cycle 1 only  
After the end of infusion  
Day 8 
± 2 days (Day 6 - 10) 
Day 15 
+ 6 days (Day 15 - 21) 
Follow-up Period 
Day 22 
+ 7 days (Day 22 - 29) 


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6.9. Vital Sign and Arterial Oxygen Saturation Measurement 
Systolic and diastolic blood pressure (mmHg), pulse rate (beats per minute), body 
temperature (°C), and percutaneous arterial oxygen saturation (SaO2) (%) by using a pulse 
oximeter will be measured, at the time points shown in Table 3. 
Table 3: Time Points of Vital Sign and Arterial Oxygen Saturation Measurement in Cycle 
 
Time Point 
Time Window 
Screening Period 
Any day between Day -28 and -1 
 
Treatment Period 
Day 1; before investigational drug 
administration  
Before the start of infusion 
Day 5; after investigational drug 
administration: Cycle 1 only  
Within 60 minutes after the 
end of infusion 
Day 8 
± 2 days (Day 6 - 10) 
Day 15 
+ 6 days (Day 15 - 21) 
Follow-up Period 
Day 22 
+ 7 days (Day 22 - 29) 
6.10. Electrocardiogram (ECG) 
A standard 12-lead ECG test will be performed to measure heart rate (min) and RR interval 
(msec), QRS interval (msec), PR interval (msec), QT interval (msec) and QT corrected 
(QTc) interval according to Fridericia's formula (msec), as well as to check for overall ECG 
findings, at the time points shown in Table 4. 
Table 4: Time Points of 12-lead ECG in Cycle 
 
Time Point 
Time Window 
Screening Period 
Any day between Day -28 and -1 
 
Treatment Period 
Day 1: 
・ 0 hour after the start of 
investigational drug 
administration 
Before the start of infusion 
 
・ 1 hour (at the end of 
infusion)  
Within 60 minutes after the 
end of infusion 
Day 5: 
Cycle 1 only  
 
 
・ 0 hour after the start of 
investigational drug 
administration 
Before the start of infusion 
 
・ 1 hour (at the end of 
infusion) 
Within 60 minutes after the 
end of infusion 
Day 8 
± 2 days (Day 6 - 10) 
Follow-up Period 
Day 22 
+ 7 days (Day 22 - 29) 


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6.11. Laboratory Tests 
6.11.1. Hepatitis Virus Screening 
The following hepatitis virus tests will be performed on any day during the screening period 
(from Day -28 to Day -1). HBV-DNA quantitative assay is not mandatory in subjects with 
negative results for both HBs antibody and HBc antibody. 
 
HCV antibody 
 
HBs antigen 
 
HBs antibody 
 
HBc antibody 
 
HBV-DNA quantification 
6.11.2. Hematology, Blood Chemistry, and Blood Coagulation Tests 
Hematology, blood chemistry and blood coagulation tests shown in Table 6 will be obtained 
at the time points shown in Table 5. Blood samples for laboratory tests should be preferably 
collected in the fasting state where possible, because laboratory tests include glucose 
measurement. 
Table 5: Time Points of Blood Collection for Hematology, Blood Chemistry, and 
Blood Coagulation Tests in Cycle 
 
Time Point 
Time window 
Screening Period 
Any day between Day -28 and -1 
 
Treatment Period 
Day 1; before investigational drug 
administration  
Before the start of infusion 
Day 5; after investigational drug 
administration: Cycle 1 only  
Within 60 minutes after the 
end of infusion 
Day 8 
± 2 days (Day 6 - 10) 
Day 15 
+ 6 days (Day 15 - 21) 
Follow-up Period 
Day 22 
+ 7 days (Day 22 - 29) 
Table 6: Test Items of Hematology, Blood Chemistry, and Blood Coagulation Tests  
Hematology 
Hemoglobin, Hematocrit, RBC count, WBC count, WBC differential,  
Platelet count 
Blood Chemistry 
Sodium (Na), Potassium (K), Chloride (Cl), Calcium (Ca),  
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), 
Alkaline phosphatase (ALP), Lactic dehydrogenase (LDH),  
Total bilirubin, Total protein, Albumin, C-reactive protein (CRP), 
Creatinine, Blood urea nitrogen, Uric acid, Glucose 
Blood Coagulation 
Prothrombin time-INR (PT-INR), Prothrombin time (PT),  
Activated partial thromboplastin time (APTT)  


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6.12. Concomitant Medication/Procedures 
Throughout the study period; from the day of obtaining the informed consent to the end of 
the follow-up period, the information listed below about concomitant medication or 
therapeutic procedures such as blood transfusion, wound care and oxygen inhalation will be 
collected. 
However, the use of dilute solutions such as water for injection or saline; which are not 
intended for treatment; except for fluid therapy to prevent or correct problems with their fluid 
and/or electrolyte status, will not be determined as concomitant medication. The use of 
antiseptic solution, cleaning agent or heparin used for preventing blood coagulation (heparin 
lock) within a cannula/catheter placed in a peripheral vein; which do not have direct effect on 
the subject’s body, will not be determined as concomitant medication. Blood transfusions 
should be determined as concomitant procedures.  
 
Medication / procedures 
 
Date started 
 
Date stopped 
 
Only for medication: total daily dose, unit and route 
 
Indication 
6.13. Adverse Events 
See Section 7. 
6.14. Lymphoma Lesions Assessment 
In this study, tumor responses will be assessed according to Revised Response Criteria for 
Malignant Lymphoma by an International Working Group to Standardize Response Criteria 
for Non-Hodgkin's Lymphomas in 2007. 
Prior to the initiation of study, the PET/CT imaging devices to be used for this study will be 
specified, and will be used throughout the study. The same device should be used for a 
series of imaging tests in an individual subject. The Central Imaging Review institution will 
radiographically assess the PET/CT imaging devices/systems prior to the study initiation 
and at any change in imaging devices at each investigational site, confirm the results of 
phantom testing, if needed, and determine the procedures of imaging tests. 
6.14.1. Baseline Assessment 
The following imaging tests and examinations will be performed during the screening period 
(from Day -28 to Day -1) for the assessment of lymphoma lesions present at baseline:  
 
Radiological assessment of tumors with contrast enhanced computed tomography 
(contrast-enhanced CT) image data at baseline 
Slice thicknesses of ≤ 5 mm will be obtained from the area covering disease lesions in 
the neck (infraorbital margin) to pelvis (femoral) region. Simple CT may be acceptable 
in a subject with known contraindication to CT contrast agents. In case that any 


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inadequate CT images are obtained for any reason, CT image data by 
Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) may be alternatively 
used. The detailed procedures/conditions of contrast-enhanced CT scan are specified 
in a separate document. 
 
Radiological assessment of tumors with FDG-PET data at baseline 
The area covering disease lesions in the neck (infraorbital margin) to pelvis (femoral) 
region will be scanned. The detailed procedures/conditions of FDG-PET scan are 
specified in a separate document. 
 
Enlargement of liver or spleen (splenomegaly and hepatomegaly) will be assessed by 
CT scan and palpation 
 
Infiltration in bone marrow will be assessed by bone-marrow biopsy (biopsy should be 
preferred whenever possible) or aspiration (clot sections)  
 
For subjects with gastrointestinal lesion: lymphoid cell infiltration will be assessed by 
endoscopy and biopsy 
 
For subjects with skin lesion: photographs of skin lesion will be taken  
Based on the radiological assessment at baseline, target lesions and non-target lesions will 
be chosen, nodal lesions or extranodal lesions will be classified, the size in 2 perpendicular 
dimensions of target lesions will be measured, the sum of the products of the greatest 
diameters (SPD) of target lesions will be calculated, and the results of FDG-PET results will 
be assessed. 
Target and non-target lesions will be selected in consideration of reproducibility at the 
subsequent assessment of radiographic tumor response in the study. When nodular lesions 
in the liver or spleen are selected as target lesions or non-target lesions, nodular mass in the 
spleen will be classified as nodal lesions; and nodular mass in the liver will be classified as 
extranodal lesions. The enlargement of liver and spleen will be separately assessed 
including assessment by palpation. 
<Target lesion> 
 
Up to 6 measurable lesions will be selected, for both enlarged lymph nodes and 
extranodal mass lesions. Larger lesions in order of the long diameter are preferred. 
See Inclusion Criteria [See Section 3.1 (5)] for the definition of measurable lesions. 
 
If one or more measurable lesions are found in a single lymph node region or a single 
organ, except for the lesion with the greatest long diameter, lesions should be selected 
from disparate regions of the body if possible. 
 
Any measurable lesions in the mediastinal or the retroperitoneal sites should be 
selected. 
<Non-target lesion> 
 
All other sites of disease present at baseline and not classified as target lesions will be 
classified as non-target lesions, including any measurable lesions that are not chosen 
as target lesions.  


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6.14.2. Tumor Response Assessment  
At the following time points, the clinical assessments and radiological assessments will be 
performed by the same examinations and imaging tests under the same procedures and 
conditions at baseline assessment, and the tumor responses will be assessed throughout 
the study. Any site of new lesion will be identified. Bone marrow assessment (biopsy or 
aspiration) will be required only if bone marrow is positive at baseline and the radiographic 
responses is judged to be CR. 
 
Any day between Day 15 and Day 21 in Cycle 3 
 
Any day between Day 15 and Day 21 in Cycle 6 
 
If administration of investigational drug is continued beyond 6 cycles, any day 
between Day 15 and Day 21 every 3 (± 1) cycles from Cycle 7 
 
If administration of investigational drug is discontinued at a cycle other than the above, 
any day between Day 15 and Day 42 in the last cycle; however, before the initiation of 
the subsequent treatment of primary disease 
According to the response criteria defined in Table 7, the local assessment of tumor 
response will be performed by the principal investigator or sub-investigator. 
Table 7: Revised Response Criteria for Malignant Lymphoma by an International Working 
Group to Standardize Response Criteria for Non-Hodgkin's Lymphomas in 2007 
 
6.14.3. Radiological Assessment at the Central Imaging Review Institution 
The principal investigator or sub-investigator (or designated staff) will submit imaging data 
by CT and FDG-PET at the following time points to the Central Imaging Review Institution. 
Details of the procedures of imaging data submission to the Central Imaging Review 
Institution are specified in a separate document.  
 
Screening period (between Day -28 and Day -1) 


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 
Any day between Day 15 and Day 21 in Cycle 3 
 
Any day between Day 15 and Day 21 in Cycle 6 
 
If the administration of investigational drug is discontinued at Cycles 1, 2, 4 and 5, any 
day between Day 15 and Day 42 in the last cycle; however, before the initiation of the 
subsequent treatment of primary disease 
The Central Imaging Review Institution will measure the tumor size of lymphoma lesions 
and evaluate FDG accumulation; according to the predefined procedure, and submit the 
radiological assessment results to the Efficacy and Safety Review Committee.  
6.15. Survival Surveillance 
6.15.1. Surveillance of Progression of Disease and Relapsed Disease  
If PD, RD or “death” is not confirmed by the end of follow-up period, tumor response 
assessment [See Section 6.14.2] will be continued at intervals of three months or less until 
PD, RD or “death” is confirmed. 
PD or RD includes not only the results of the radiological assessment with imaging data but 
also “symptomatic progression” at the principal investigator’s or sub-investigator’s 
judgement based on clinical symptoms or laboratory findings, etc. The development of 
secondary cancer is not defined as progression event, and surveillance of PD, RD or “death” 
will be continued. 
6.15.2. Surveillance of Subsequent Treatment for Primary Disease 
Throughout the survival surveillance period [See Section 6.15.3], the information of 
subsequent treatment for primary disease; e.g., antitumor chemotherapy, antitumor 
immunotherapy, radiotherapy, and hematopoietic stem cell transplant; including the name of 
medications, the date of treatment initiation and the tumor responses will be surveyed. 
6.15.3. Survival Surveillance 
A survival surveillance will be continued, at intervals of six months or less whenever possible, 
for up to 2 years from the date of initiation of investigational drug administration (Day 1 of 
Cycle 1) to confirm “survival” or “death” of subjects. When the subject’s death is confirmed, 
the “date of death” or “the most recent date (date of the last day) of survival confirmation” 
should be specified. The surveillance via telephone is allowed. 
6.16. Pharmacokinetics 
Pharmacokinetics (PK) assessment will be performed only in Cycle 1 only at the 
investigational sites where the principal investigator has agree to perform PK assessment in 
advance. The remaining portion of samples after the completion of determination of drug 
concentration will be appropriately discarded at a central laboratory. 
6.16.1. Blood Collection for Determination of Drug Plasma Concentration 
At the time points shown in Table 8, blood samples (approximately 10 mL containing ≥4 mL 


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of plasma) for determination of plasma drug concentration will be collected from a vein of 
forearm of the opposite arm of the infusion site. The collected blood samples will be 
processed at the investigational sites and then submitted to the central laboratory according 
to a specific procedure. The detailed procedures of blood collection, sample processing and 
submission are specified in a separate document, and will be provided to the investigational 
sites together with a set of sample collection kits including tubes for blood collections and 
containers for shipment. 
At the central laboratory, plasma concentration of arsenic, darinaparsin and its metabolites 
will be analyzed. The results of analysis will be reported to the investigational sites by the 
Sponsor or CRO.  
Table 8: Time Points of Blood Collection for Drug Plasma Concentration in Cycle 1 
Time Point 
Time window 
Day 1: 
0 hr after the start of investigational drug 
infusion, 
Within 60 min prior to the start of 
infusion 
1 hr (immediately after the end of infusion), 
Within 15 min after the end of infusion 
2 hrs (1 hr after the end of infusion), 
± 15 min 
4 hrs (3 hrs after the end of infusion), 
± 15 min 
6 hrs (5 hrs after the end of infusion), 
± 30 min 
8 hrs (7 hrs after the end of infusion). 
± 30 min 
Day 2: 
0 hr 
Within 60 min prior to the start of 
infusion 
Day 3: 
0 hr 
Day 4: 
0 hr 
Day 5: 
0 hr after the start of investigational drug 
infusion, 
Within 60 min prior to the start of 
infusion 
1 hr (immediately after the end of infusion), 
Within 15 min after the end of infusion 
2 hrs (1 hr after the end of infusion), 
± 15 min 
4 hrs (3 hrs after the end of infusion), 
± 15 min 
6 hrs (5 hrs after the end of infusion), 
± 30 min 
8 hrs (7 hrs after the end of infusion). 
± 30 min 
Day 6: 
Same time of the infusion start on Day 5 
± 60 min 
Day 8: 
Same time of the infusion start on Day 5 
± 60 min 
Day 15: 
 
+ 6 days (Day 15 - 21) 
6.16.2. Urine Collection for Determination of Drug Urine Concentration 
At the time periods shown in Table 9, the entire urine will be accumulated in Cycle 1. The 
urine accumulation will be started after the subject completely urinates, and completed after 
the subject completely urinates during each time period of urine collection. 


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After the measurement of a total volume (mL) of urine collected at each time period, ≥ 20 mL 
of urine will be taken in the container and submitted to the central laboratory according to a 
specific procedure. The detailed procedures of urine collection, sample processing and 
submission are specified in a separate document, and will be provided to the investigational 
sites together with a set of sample collection kits including containers for shipment.  
At the central laboratory, urine concentration of arsenic, darinaparsin and its metabolites will 
be analyzed. The results of analysis will be reported to the investigational sites by the 
Sponsor or CRO. 
Table 9: Time Periods of Urine Collection for Drug Urine Concentration in Cycle 1 
Time Periods 
Time window 
Day 1: 
Start of urine accumulation 
0 hr from the start of 
infusion 
Within 60 min prior to the 
start of infusion 
 
~ End of urine accumulation 
For 4 hrs (3 hrs after the 
end of infusion) 
± 15 min 
 
Start of urine accumulation 
4 hr from the start of 
infusion 
Day 2: 
~ End of urine accumulation 
Until 24 hrs after the 
start of infusion on Day 1 
Within 60 min prior to the 
start of infusion on Day 2 
Day 5: 
Start of urine accumulation 
0 hr from the start of 
infusion 
Within 60 min prior to the 
start of infusion 
 
~ End of urine accumulation 
For 4 hrs (3 hrs after the 
end of infusion) 
± 15 min 
 
Start of urine accumulation 
4 hr from the start of 
infusion 
Day 6: 
~ End of urine accumulation 
Until 24 hrs after the 
start of infusion on Day 5 
± 60 min of same time of 
the infusion start on Day 5  


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6.17. Reference: Volume of Blood Sample Collection 
As shown in Table 10, Table 11 and Table 12, the standard blood sample collection volume 
from the screening period to the end of Cycle 1 is 42-47 mL per subject who are not subject 
to drug plasma PK assessment and 222-227 mL per subject who are subject to the 
assessment. The standard volume in each cycle from Cycle 2 is 24 mL and 8 mL in the 
follow-up period. When a subject completes the study at the end of 6 cycles, the standard 
volume is approximately 170-175 mL in a subject who is not subject to drug plasma PK 
assessment and 350-355 mL in a subject who is subject to the assessment. 
Table 10: Blood Sample Collection Volumes from Screening Period to Cycle 1 
Test Items 
Volume of Blood Sample 
Collection per Time Point 
(approximately) 
Frequency 
Subtotal 
Volume 
Hepatitis virus 
2-7 mL 
x 1 
2-7 mL 
Hematology 
2 mL 
x 5 
10 mL 
Clinical chemistry 
4 mL 
x 5 
20 mL 
Blood coagulation 
2 mL 
x 5 
10 mL 
Determination of Drug 
Plasma Concentration 
10 mL 
x 18 
180 mL 
Total Volume 
Blood Collection for 
Determination of Drug 
Plasma Concentration 
No 
42 - 47 mL 
Yes 
222 - 227 mL 
Table 11: Blood Sample Collection Volumes in Each Cycle from Cycle 2 
Test Items 
Volume of Blood Sample 
Collection per Time Point 
(approximately) 
Frequency 
Subtotal 
Volume 
Hematology 
2 mL 
x 3 
6 mL 
Clinical chemistry 
4 mL 
x 3 
12 mL 
Blood coagulation 
2 mL 
x 3 
6 mL 
Total Volume 
24 mL 
Table 12: Blood Sample Collection Volumes in Follow-up Period 
Test Items 
Volume of Blood Sample 
Collection per Time Point 
(approximately) 
Frequency 
Subtotal 
Volume 
Hematology 
2 mL 
x 1 
2 mL 
Clinical chemistry 
4 mL 
x 1 
4 mL 
Blood coagulation 
2 mL 
x 1 
2 mL 
Total Volume 
8 mL 


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7. 
SAFETY DATA COLLECTION AND REPORTING 
7.1. Definitions 
7.1.1. 
Adverse Events 
An adverse event (AE) is defined as “any untoward medical occurrence in a subject 
administered an investigational drug and which does not necessarily have a causal 
relationship with this treatment”.  
This definition of AEs includes any such medical occurrences or exacerbation of pre-existing 
medical conditions or events (primary disease, underlying disease or concurrent diseases 
etc.). Obvious exacerbation of the pre-existing medical conditions; worsening in severity, 
increase in frequency, or extending of duration of the events, in the judgment of the principal 
investigator or sub-investigator, will qualify as an AE. 
The principal investigator or sub-investigator will identify a “term” of diagnosis or syndrome 
of the AE as much as possible. Diseases or clinical signs with accompanying symptoms, the 
diseases or clinical signs will be identified and qualified as AEs. 
The principal investigator or sub-investigator is responsible to confirm the changes in 
laboratory test results (vital signs, ECGs, laboratory test values, etc.) from baseline values 
in an individual subject. The clinically significant abnormal changes; including any change 
for which a new treatment or alternative treatment, in the judgment of the principal 
investigator or sub-investigator, will qualify as AEs. Diseases or clinical sings accompanying 
abnormal laboratory findings, the diseases or clinical signs will qualify as AEs. 
7.1.2. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an adverse event that 
 
is fatal 
 
is life threatening (an event that places the subject at immediate risk of death) 
 
requires inpatient hospitalization or prolongation of existing hospitalization 
 
results in persistent or significant disability/incapacity 
 
is a congenital anomaly/birth defect 
 
is any other medically important condition 
A hospitalization meets the regulatory definition for “serious” is any inpatient hospital 
admission that includes a minimum of an overnight stay in a health care facility. A 
hospitalization only for the previously scheduled treatment or examination (operations or 
medical tests planned in advance) will not qualify as an AE. 
Any AE that does not clearly meet one of the definitions above may be considered by the 
principal investigator or sub-investigator whether the event meets the criteria of “any other 
medically important condition” in the definitions of a SAE. 


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7.2. Procedures for Adverse Events Reporting 
The principal investigator or sub-investigator (or designated staff) will collect and identify the 
following information on AEs during the period from the start of investigational drug 
administration to the end of follow-up period, and enter a description of the event into the 
eCRF. 
 
Term of adverse event 
 
Date of onset 
 
Seriousness; serious or not serious 
 
Severity 
 
Relationship to the investigational drug; if “No,” the reason for “No” 
 
Any action taken; if “Yes,” the details of the action 
 
Outcome and date of outcome confirmation (date of resolution, date of confirmation or 
examination of resolving/not resolved events, date of death, etc.)  
Relationship (Causality) 
Relationship of an AE to the investigational drug should be assessed from the point of view 
that “there is a reasonable possibility that the investigational drug caused the AE”. The 
principal investigator or sub-investigator should determine either of “Yes” or “No”. 
Severity Assessment 
Severity of an AE will be assessed by the principal investigator or sub-investigator, using the 
5-grade scale according to NCI-CTCAE Version 4.0. For those events not found in 
NCI-CTCAE Version 4.0, the principal investigator or sub-investigator will clinically 
determine the severity based on the definition in Table 13.  
7.3. Follow-up Observation of Adverse Events 
Investigational-drug-related AEs that are ongoing at the end of follow-up period will be 
followed, in case that the principal investigator or sub-investigator judges the follow-up 
observation of AEs is clinically required. 
The follow-up observation of AEs will be continued for 4 weeks after the end of follow-up 
period, and “date of resolution/resolving of AE” or ”date of subject’s death” will be specified 
as the date of outcome confirmation.  
If an AE has not resolved (have not been resolving or become stable) within 4 weeks after 
the end of follow-up period, the day of the first observation of AEs during the period 
≥ 4 weeks after the end of following-up period will be specified as the date of outcome 
confirmation. 


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Table 13: Adverse Event Grading (Severity) Scale 
Grade 
Description 
Grade 1 (Mild)  
・ Mild 
・ Asymptomatic or mild symptoms 
・ Clinical or diagnostic observations only 
・ No intervention indicated 
Grade 2 (Moderate)  
・ Moderate 
・ Minimal, local or noninvasive intervention indicated 
・ Limiting age-appropriate instrumental Activities of Daily 
Living (ADL)*1 
Grade 3 (Severe)  
・ Severe or medically significant but not immediately 
life-threatening 
・ Hospitalization or prolongation of hospitalization indicated 
・ Disabling 
・ Limiting self care ADL*2 
Grade 4 (Life-threatening)  ・ Life-threatening consequences 
・ Urgent intervention indicated 
Grade 5 (Death)  
・ Death related to AE 
*1:  Instrumental ADL; refers to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
*2:  Self care ADL; refers to bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden 
7.4. Reporting of Serious Adverse Events 
The principal investigator or sub-investigator (or designated staff) must submit an initial SAE 
report of any SAE to the Sponsor or CRO with any means of contact within 24 hours since 
knowing of the event.  
The principal investigator must submit the follow-up SAEs report about the information on 
SAEs. A form provided in advance by the Sponsor or CRO or a form designated by the 
investigational site must be used, and submitted to the Sponsor or CRO, and the 
investigational site or site IRB. Follow-up SAE report will include any additional information 
or change in the information recorded in previous reports.  
For contact information of the Sponsor and CRO, see “Organization and Structure of Clinical 
Study in Each Country and Region.” 
 


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8. 
DATA COLLECTION AND MANAGEMENT 
8.1. Data Entry to Electronic Case Report Form (eCRF) 
The principal investigator or sub-investigator (or designated staff) enters protocol-specified 
data into the eCRF by using the EDC system in this study; in an accurate, complete and 
easy-to-read manner at appropriate times, in English in principle. The study collaborators, 
other than the sub-investigator, who are designated by the principal investigator will be 
allowed only to transcribe data from the source documents into eCRF.  
The principal investigator will review the data in eCRF, confirm the completeness and 
accuracy of data, and then provide an electronic signature in the predefined form in eCRF. 
In accordance with the investigational institution’s own policy, the eCRF data that are 
exported in PDF will be retained at the site.  
8.2. Correction or Change to Data in eCRF 
If the principal investigator or sub-investigator (or designated staff) makes changes or 
corrections to data in the eCRF, the information on the former data before changes or 
corrections, persons who make changes or corrections, and date on which changes or 
corrections are made will be recorded in the audit trail in the EDC system. In any change or 
correction in the important data such as the date of obtaining the informed consent or the 
relationship between investigational drug and AEs, the reason for data changes or 
corrections should be specified and entered in eCRF. 
The principal investigator will review the changes or corrections to data in the eCRF, confirm 
the data to be complete and accurate, and then provide an electronic signature in the 
predefined form in eCRF. In accordance with the investigational institution’s own policy, the 
audit trail that is exported in PDF will be retained at the site. 
The Development Sponsor or the data management CRO should review the data in eCRF in 
terms of data consistency, omission or apparent contradiction, or violation of GCP or the 
protocol. For a question resulting from the review, a query for a given data on eCRF will be 
created and sent to an investigational site. The principal investigator or sub-investigator (or 
designated staff) will respond to the queries by re-investigation and making changes or 
correction to data in eCRF if needed. 
In this study, the changes or corrections to data in eCRF will not be made by a person 
designated by the Development Sponsor.  
8.3. Data in eCRF as Source Data 
The data entered in eCRF should match exactly the corresponding written record in source 
documents. The principal investigator will create a record that explains the reason for any 
inconsistency.  
The data entered in eCRF may be qualified as the source documents, if a given data on 
eCRF itself is only source data; i.e., no written or electronic source document is existing. In 
this study, the data in eCRF may be qualified as source data if no source document exists 
for the items listed below and all of relevant comments:  


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 
Subject background: ethnic background/race 
 
Primary disease: 
- 
Clinical symptoms caused by the primary disease (clinical symptoms associated 
with primary disease) 
- 
Clinical stage by the Ann Arbor classification 
- 
Prognostic risk group by International Prognostic Index (IPI)  
- 
Prognostic risk group by Prognostic Index for T-cell lymphoma (PIT) 
 
Medical history: 
- 
Concurrent diseases at the start of investigational drug dosing 
- 
Severity of drug sensitivity or allergy 
 
Pregnancy test: reason for the absence of pregnancy test 
 
12-lead ECG: overall ECG findings (presence of abnormalities)  
 
Concomitant procedures: reason for starting therapeutic procedures  
 
Adverse Events (AEs): 
- 
Severity 
- 
Seriousness  
- 
Relationship to the investigational drug  
- 
Reason/rationale for denying the relationship  
8.4. Deviations from the Protocol 
The principal investigator or sub-investigator (or designated staff) should keep a record of all 
actions deviating from the protocol for any reason. 
The principal investigator or the investigational site may deviate from or modify the protocol 
for medically justifiable reasons, without prior written agreement with the Sponsor and prior 
written IRB approval, such as when necessary to eliminate imminent hazards to the subject. 
However, the principal investigator should subsequently take procedures according to the 
regulatory requirements of each country or region in an expedited manner.  
8.5. Committees and Coordinating Investigators 
8.5.1. 
Pathological Review Committee 
The Pathological Review Committee will consist of multiple pathologists who are not 
responsible for a medical expert, principal investigator or sub-investigator, coordinating 
investigator, or a member of another committee of this study. The Committee will be charged 
with the following tasks.  
 
Guidance and advice for the protocol and procedure for a central pathological 
diagnosis  
 
Guidance and advice for the procedures at central laboratory activities where 
pathology specimens are collected, stored and unstained tissue specimens are 
stained.  
 
Staining of unstained samples as needed  


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 
Diagnosis by each member of the Pathological Review Committee (individual 
diagnosis)  
 
Central pathological diagnosis by the Pathological Review Committee (consensus 
diagnosis)  
The histopathological classification based on World Health Organization (WHO) 
Classification Version 4 (2008) is used for the central pathological diagnosis at the 
Pathological Review Committee. If the central pathological diagnosis at the Pathological 
Review Committee differs from that at each investigational site, the central pathological 
diagnosis at the Pathological Review Committee will be given priority.  
8.5.2. 
Efficacy and Safety Review Committee 
The Efficacy and Safety Review Committee will consist of the hematologists and radiologists 
who are not responsible for a medical expert, principal investigator or sub-investigator, 
coordinating investigator, or a member of another committee of this study. The Committee 
will be charged with the following tasks. 
 
Guidance and advice for the protocol and procedure for a central assessment of tumor 
response  
 
Guidance and advice for the procedures at the Central Imaging Review Institution  
 
Central review based on the results of radiological assessment of tumor response at 
the Central Imaging Review Institution and the results of a local assessment of tumor 
response based on “non-imaging data” at each investigational site.  
 
Overall evaluation of efficacy and safety 
 
Advice for the termination/suspension of the study (appropriateness of continuation of 
the study)  
The Efficacy and Safety Review Committee will be held to perform an interim review of 
efficacy and safety (and pharmacokinetics as needed) at the point when the number of 
subjects evaluable for efficacy reaches 20 and have all necessary data available.  
8.5.3. 
Coordinating Investigators 
At each country or region, in principle, at least one coordinating investigator will be assigned. 
The coordinating investigators will be charged with the following tasks, at request of the 
Development Sponsor. No committee will be organized.  
 
Guidance and advice for protocol development and revision 
 
Coordination among different countries/region participating in this study as for the 
content of protocol 
 
Coordination among different countries/region in this study as for interpretational 
questions about the protocol 


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9. 
STATISTICAL CONSIDERATIONS 
9.1. Subsets 
9.1.1. 
Handling of Subjects and Data 
Prior to the analysis, the Development Sponsor will determine the handling (inclusion) of 
subjects based on the consultation with medical experts. If it is considered that data 
including laboratory values, 12-lead ECG or drug plasma or urine concentration 
measurements has been affected by abnormality of a sample (e.g. hemolysis or milky fluid) 
or a technical error, the Development Sponsor will decide, prior to the data analysis, whether 
or not to exclude that data from analysis based on the consultation with medical specialists. 
9.1.2. 
Efficacy Analysis Set 
A subject group consisting of subjects who fulfill eligibility criteria [See Section 3.1] and who 
take a tumor response assessment [See Section 6.14.2] at least one time after the 
administration of the investigational drug is defined as a “Full Analysis Set (FAS)”. A subject 
group consisting of subjects who have no important protocol deviation including violation of 
eligibility criteria and/or dose and dosage that may affect the efficacy evaluation is defined 
as “Per Protocol Set (PPS)”. FAS will be used for the primary analysis of efficacy endpoints, 
and PPS will be used for the secondary analysis of efficacy endpoints.  
9.1.3. 
Safety Analysis Set 
A group of subjects who receive at least one dose of investigational drug is defined as the 
“safety analysis set”. The safety analysis set will be used for the analysis of safety 
endpoints.  
9.1.4. 
PK Analysis Set 
The “PK analysis set” will consist of all subjects who receive at least one dose of 
investigational drug and have at least one point of drug plasma or urine concentration data. 
PK analysis set will be used for the analysis of PK endpoints. 
9.2. Sample Size Considerations 
The required sample size of 55 is calculated in SAS® POWER Procedure using Fisher's 
exact test, when the one-sided significance level is 5% with a statistical power of 90%, with 
the expected overall response rate (ORR) of 25% and the 10% threshold. Considering for 
the subjects who are excluded from analysis resulting from the central pathological 
diagnosis, the planned sample size is 65 subjects. 
9.3. Interim Analysis 
No interim analysis and no early termination for efficacy are planned in this study. 
An interim review for efficacy and safety including PK as needed [See Section 8.5.2] will be 
performed at the point when the number of efficacy evaluable subjects evaluable for efficacy 
reaches 20 and have all necessary data available. 


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9.4. Planned Methods of Analysis 
Upon submission of the New Drug Application for SP-02L, an appropriate data cut-off date 
should be determined as the primary endpoint is evaluable. Detailed analytical method in 
this study will be specified in the statistical analysis plan. 
In this study, no analysis will be performed considering withdrawal. No imputation for 
missing values will be performed. No adjustment for covariates, the investigational sites or 
multiplicity will be performed.  
9.4.1. 
Data summarization 
Of the demographic variables and baseline (subject background factors) and data, 
continuous variables will be summarized by n, mean, standard deviation (or standard error 
for efficacy), median, Q1, Q3, minimum, and maximum values. Categorical variables will be 
summarized by frequency and percentage. 
9.4.2. 
Analysis of Efficacy Endpoints (Tumor Response) 
Based on a central assessment of tumor response at Efficacy and Safety Review 
Committee, the best overall responses for 6 cycles will be summarized to calculate the ORR 
and 90% confidence interval (90% CI). Based on a local assessment at each investigational 
site, the best overall responses for 6 cycles and in the entire period will be summarized to 
calculate ORR and 90% CI. 
The best overall response will be summarized and the ORR will be calculated by 
histopathological classification, clinical stage according to Ann Arbor classification ，
prognosis risk group according to international prognostic index (IPI), prognosis risk group 
based on Prognosis Index for T-cell lymphoma (PIT), ethnic background, sex and age 
(< 61 years old or ≥ 61 years old).  
To assess the tumor response in each subject, the waterfall plot will be produced to show 
the rate of tumor shrinkage at best overall response. 
9.4.3. 
Analysis of Efficacy Endpoints (Survival Time and Others)  
Progression-free survival (PFS), time to response (TTR), duration of response (DOR) and 
overall survival (OS) will be summarized overall and by histopathological subtype. PFS and 
OS will be analyzed by using Kaplan-Meier method overall and by histopathological subtype. 
Progressive disease (PD), relapsed disease (RD) or death which occurs earlier is defined as 
“progression event”, and “the date of progression” will be identified for analyses of PFS and 
DOR in accordance with the following rules: 
 
The date of judgment of PD or RD based on the radiological assessment of tumor 
response [See Section 6.14.2] is defined as “the date of progression”. 
 
PD or RD includes not only the results of radiological assessment with imaging data 
but “symptomatic progression” at the principal investigator’s or sub-investigator’s 
judgement based on clinical symptoms or laboratory findings, etc. In this case, the 
date of the investigator’s judgement is defined as “the date of progression”. 


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 
If “death” occurs earlier than the judgement of “PD” or “RD”, the date of death is 
defined as “the date of progression”. 
If no progression event is confirmed prior to the following events, the most recent date (date 
of the last day) of radiological assessment of tumor response [See Section 6.14.2 will be 
defined as “the date of censoring”: 
 
Subsequent anticancer treatment for primary disease initiated 
 
Investigational drug is discontinued for toxicity (investigational-drug-related AEs) 
 
Subject is lost to follow up 
If a subject is surviving on the date of “data cut-off”, the most recent date (date of the last 
day) of confirmation of subject’s existence is defined as “the date of censoring” for the 
analysis of OS. For a subject lost to follow-up, the last date when the subject’s existence is 
confirmed prior to the subject’s lost to follow-up is defined as “the date of censoring”.  
9.4.4. 
Analysis of Safety Endpoints 
The incidence of AEs will be summarized by system organ class and by preferred term 
according to the ICH-MedDRA, and by ethnic background and severity. Incidence of 
investigational-drug-related AEs, serious AEs (SAEs) and investigational-drug-related SAEs 
will be also summarized, respectively, in the same way. 
SAEs, SAEs of ≥ Grade 3, and significant AEs in the judgement of the Development Sponsor; 
e.g. neurological disorder and psychiatric disorder, will be summarized or described. 
Vital signs, laboratory values and ECG parameters will be summarized by item and time point. 
9.4.5. 
PK Analysis 
Plasma drug concentrations will be summarized overall and by ethnic background, and the 
graphs of mean plasma drug concentration-time profiles will be provided. The following PK 
parameters for each subject will be estimated using non-compartmental methods and 
summarized overall and by ethnic background. 
 
Maximum drug concentration time: tmax 
 
Maximum drug concentration: Cmax 
 
Area under the blood concentration time curve: AUC0-t and AUC0-∞ 
 
Half-life period: t1/2 
 
Systemic clearance: CL 
 
Distribution volume: Vdss and Vdz 
 
Mean retention time: MRTlast 
Urine excretion rates will be calculated and summarized overall and by ethnic background.  
9.4.6. 
Additional Analyses 
At the discretion of the Development Sponsor, additional analyses of the data will be 
conducted as deemed appropriate. Details of additional analyses are specified in the 
statistical analysis plan.  


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10. STUDY ADMINISTRATION AND ETHICAL CONSIDERATIONS  
10.1. General Ethical Requirements 
This study will be conducted in accordance with the ethical principles of the Declaration of 
Helsinki, 
ICH-GCP, 
country- 
and 
region-specific 
GCP, 
the 
currently 
approved 
protocol/amendment(s) of this study, the clinical trial contract that is concluded between 
each investigational site and the Sponsor (and CRO), and other agreements that are 
concluded between the medical institution and the Sponsor (and CRO). 
10.2. Protocol Management 
The Sponsor provides the protocol and an example of informed consent form, and sample 
of eCRF as needed to the principal investigator. Any amendment of these documents will be 
promptly notified to the principal investigator with the reason for amendment, except when 
necessary to eliminate immediate hazards to the subjects [See Section 8.4] or when the 
change(s) involves only logistical or administrative aspects of the trial (e.g., change of the 
name or address of investigational site, name and title of principal investigator, name and 
address of the Sponsor or CRO, and name, title and contact information of monitors) 
The Sponsor should obtain the principal investigator’s agreement for the protocol or 
amendments if the protocol is amended and to conduct the study in compliance with the 
protocol. To confirm this agreement, the Sponsor and investigator will sign and date on the 
page of “Investigator’s Agreement” in the protocol or any alternative document. The Sponsor 
will designate a Study Manager in each of participating country or region as a person who is 
authorized to represent the Sponsor and sign the above document.  
10.3. Quality Control and Quality Assurance 
The Sponsor and CRO are responsible for implementing and maintaining quality assurance 
and quality control systems with written SOPs. 
10.3.1. Monitoring and Audit 
Monitors will visit the investigational sites and carry out the monitoring. The purposes of 
study monitoring are to verify that the rights, safety and well-being of human subjects are 
protected, the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s), and 
the data entered in eCRF and in other study reports are accurate, complete and verifiable 
from source documents.  
The auditors should evaluate study conduct and compliance with GCP and the protocol, as 
quality control functions, according to the audit plan. The observations and findings of the 
auditor(s) should be documented and submitted to the Sponsor. A global auditor who is 
appointed by the Development Sponsor may visit the CROs and the investigational sites in 
each country or region to evaluate study conduct in each country or region to confirm the 
compliance of the study with the ICH-GCP from a unified perspective (Global Audit).  


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10.3.2. Direct Access to Source Documents 
The principal investigator and medical institutions are required to permit direct access to all 
study-related documents, data, and records, including source documents related to the 
subject’s original medical records and data, on the occasion of monitoring and auditing by 
the Sponsor or CRO as well as the inspection by the IRB or domestic and foreign regulatory 
authorities. The principal investigator or sub-investigator is obligated to inform and obtain 
the written consent of each subject to permit the direct access to the subject’s source 
documents related to the subject’s original medical records and data, on the occasion of 
monitoring and audit as well as the site inspection by the IRB or regulatory authorities. 
10.4. Retention of Study Records 
The principal investigator and the investigational site, including IRB and person in charge of 
the management of the investigational drug, should not destroy, without prior agreement 
with the Sponsor or CRO, any study-related documents or records, in conformance with 
ICH-GCP and country- or region-specific GCP.  
The Sponsor or CRO should notify the principal investigator or the investigational site in 
writing when these documents no longer need to be retained (at the end of retention period). 
10.5. Subject Confidentiality 
The principal investigator and the investigational site must ensure that subject’s 
confidentiality is maintained as follows:  
 
On data, documents and records submitted to the Sponsor or CRO, such as data 
entered into eCRFs and the Serious Adverse Events Reports, a subject should be 
identified by a subject number only.  
 
Data and documents that are not for submission to the Sponsor or CRO, including 
signed informed consent forms, should be kept in strict confidence at the 
investigational site. 
Employees of the Sponsor and the CRO, whether incumbent or not, should not disclose, 
without legitimate reasons, any confidential information obtained through direct access to 
the source documents. 
10.6. Health Damage Compensation 
Subjects will receive compensation for any study-related health damage caused to them in 
compliance with “Compensation for Health Damage on Subjects” that is a separate 
document prepared by the Sponsor in each country or region. The Sponsor will purchase 
health insurance as an action for performance of liability for compensation and liability 
indemnity, as necessary. 


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10.7. Publication 
If the entire results obtained from this study are to be disclosed (submission of paper/article, 
publication of book or presentation at professional meetings, etc.), the Development 
Sponsor will decide the authorship or presenter, based on the discussion with medical 
experts, in accordance with the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals (International Committee of Medical Journal Editors). A copy of any 
publication or written presentation of the data or script of any oral presentation of the data 
must be provided to the Development Sponsor for review and approval prior to submission 
for publication or presentation, including abstracts for professional meetings. 
If any specific data on individual subject at each investigational site is to be published, the 
author or presenter will have discussion, in advance, with the Sponsor about the contents. 


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11. REFERENCES 
 
 
Darinaparsin Investigator’s Brochure 
 
International T-Cell Lymphoma Project: International Peripheral T-Cell and Natural 
Killer/T-Cell Lymphoma Study: Pathology Findings and Clinical Outcomes. J Clin Oncol 
2008, 26: 4124-4130 
 
NCCN Clinical Practice Guidelines in Oncology - Non-Hodgkin's Lymphomas Version 2, 
2015. http://www.nccn.org 
 
Swerdlow SH, Campo E, Harris NL, et al.: WHO classification of tumours of 
haematopoietic and lymphoid tissues, fourth edition. Lyon, France: IARC; 2008 
 
Cheson BD, Pfistner B, Juweid ME, et al.: Revised Response Criteria for Malignant 
Lymphoma. J Clin Oncol 2007, 25; 579-586 
 
Edited by Japanese Society of Hematology, Japanese Society for Lymphoreticular 
Tissue Research: General Rules for the Clinical and Pathological Studies on Tumors of 
Hematopoietic and Lymphoid Tissues, First Edition: March 31, 2010. 
 
Drafting Committee for Hepatitis Management Guidelines and the Japan Society of 
Hepatology: JSH Guidelines for the Management of Hepatitis B Virus Infection. 
Hepatology Research 2014, 44; 1-58 
 
Guidelines on the Clinical Evaluation of Antineoplastic Agents, PFSB/ELD Notification 
No. 1101001, dated November 1, 2005. 
 
U.S. Department of Health and Human Services, Food and Drug Administration, Center 
for Drug Evaluation and Research, Center for Biologics Evaluation and Research: 
Guidance for Industry - Clinical Trial Endpoints for the Approval of Cancer Drugs and 
Biologics. May 2015 
 


Product: SP-02L 
Appendix 1 
Protocol Number: SP-02L02 
Date: 24 January 2020 
 
CONFIDENTIAL 
 
Solasia Pharma K.K. 
Appendix 1: ECOG Performance Status Scale 
Score 
Description 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light 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 
 
 


Product: SP-02L 
Appendix 3 
Protocol Number: SP-02L02 
Date: 24 January 2020 
 
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Appendix 2: Pharmacy Guide 
1. 
Packaging and Formulation 
The investigational drug will be supplied as a sterile, white to off-white, lyophilized powder in 
glass vials containing 150 mg of darinaparsin per vial. Each vial and box will be labeled 
according to country- and region-specific regulations, and each box will have 10 vials of 
investigational drug. The label will comply with local regulations. 
2. 
Labeling 
A box and each vial of investigational drug will be properly labeled identifying the limited use 
to clinical study, name of the investigational drug, lot number, name and address of the 
sponsor, appropriate storage conditions, and appropriate country- and region-specific 
caution statement. 
3. 
Storage and Expiry Date  
The investigational drug should be stored under refrigeration at 2°C to 8°C (36°F to 46°F), 
except when being prepared for injection. 
The expiry date of the investigational drug will be notified in writing by the Sponsor or CRO 
based on the results of stability studies that is being conducted concurrently with this study.  
4. 
Calculation of Administration Dose 
The dose (mg) of the investigational drug given to each subject will be calculated by 
multiplying the subject’s body surface area (BSA, m2) by 300 (mg). The maximum dose will 
be 600 mg; a dose exceeding 600 mg per body must not be administered. 
The BSA will be calculated using DuBois’s formula shown below, based on the subject’s 
height (cm) and body weight (kg) measured during the screening period. 
S ＝ W0.425 × H0.725 × 0.007184 
S: Body surface area (m2) 
W: Weight (kg) 
H: Height (cm) 
 
If there are ±10% changes in the body weights measured on Day 1 of each cycle (before the 
start of investigational drug administration) from the weight measured in the screening 
period, BSA will be re-calculated to adjust the dose.  
5. 
Preparation 
The preparation of investigational drugs will be performed at each investigational site by 
using aseptic techniques at room temperature. 
Since SP-02L is a cytotoxic antitumor drug, handling of the drug should strictly comply with 
precautions as required for the handling of toxic chemicals. Protectors (goggles, gloves, 
masks, etc.) are required at the preparation. If the drug or drug solution attached to the skin, 


Product: SP-02L 
Appendix 3 
Protocol Number: SP-02L02 
Date: 24 January 2020 
 
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the attached area should be washed well with soap and water immediately and if to the 
mucosa, rinsed well immediately. If the drug solution spills out, it should be wiped out with 
an absorbable material and the area should be cleaned with water and alcohol more than 
three times.  
Each vial contains 150 mg of darinaparsin. When completely reconstituted with 2.0 mL 
water for injection, the nominal concentration is 75 mg/mL. Within 1 hour of reconstitution, 
the required dose (mg) is drawn into at least one syringe and added to an infusion bag 
containing 250 mL of saline solution (Sodium Chloride Injection). 
In case that a lot number of investigational drug is multiple at the investigational site, the 
investigational drugs of the same lot number will be used in a subject throughout a cycle 
whenever possible; a subject will not receive the investigational drug of multiple lot numbers 
within a cycle. 
6. 
Administration 
The investigational drug will be reconstituted and diluted according to the preparation 
procedures described in above 5, and will be given intravenously over 1 hour (± 10 minutes) 
on each day of administration. After the infusion, a flushing with a sufficient amount of saline 
will be done to ensure all the drug remaining in the infusion route is infused fully to the 
subject. 
Since the injection site abnormalities have been frequently reported in subjects who 
received the investigational drug via a peripheral line in the previous clinical studies, the 
administration of the investigational drug is recommended to be given through the central 
vein (e.g., via an implantable subcutaneous infusion port, a central venous catheter, a 
peripherally inserted central venous catheter). If any abnormal finding at the injection site is 
observed during the infusion via a peripheral line, the administration will be held at the 
discretion of the principal investigator or sub-investigator. Saline may be infused via a 
three-way stopcock. The IV infusion may be given from another peripheral vein or via a 
central venous line or port.  
The following matters should be noted when the investigational drug is administered: 
 
During the injection via a peripheral line, full care should be taken to avoid 
extravasation. If any extravasation is observed, the dose will be held immediately, 
medical procedures will be provided for it, and a change in the peripheral vein for IV 
infusion will be considered.  
 
No other drug for injection should be given concurrently via the same IV line. 
 
The investigational drug administration will be started at the same time as much as 
possible in subjects for pharmacokinetic assessment in Cycle 1. 
Destruction of Used Investigational Drugs 
Used investigational drugs and boxes (empty boxes) will be destroyed locally in accordance 
with the investigational site’s policy. The local destruction of used investigational drugs will 
be documented, as needed, according to the investigational site’s policy. In case that the 
investigational site is incapable of local destruction of used investigational drugs and empty 


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Protocol Number: SP-02L02 
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boxes, the detailed procedures of destruction will be specified in the procedure manual of 
investigational drug management. 
7. 
Supply and Return of Drug 
After the conclusion of the clinical trial contract, the Sponsor will ship investigational drugs, 
via CRO or an investigational drug delivery service company, to the person in charge of the 
investigational drug management (e.g. pharmacist) at the investigational site. On receipt of 
the investigational drugs, the person in charge of the investigational drug management will 
conduct an inventory of the supplies and check condition of drugs. Also a “Proof of Receipt 
of Investigational Drug” should be completed and submitted to the Sponsor and a “Proof of 
Delivery of Investigational Drug” should be retained at the investigational site. 
At the end of study, or as otherwise directed, the Sponsor will collect unused investigational 
drugs, via CRO or an investigational drug delivery service company. On return of unused 
investigational drugs, the person in charge of the investigational drug management will 
complete the check of amount and condition of unused drugs. A “Proof of Return of 
Investigational Drug” must be completed and submitted to the Sponsor, and a “Proof of 
Collection of Investigational Drug” should be retained at the investigational sites.  
8. 
Investigational drug Accountability 
The person in charge of the investigational drug management will prepare an 
“Investigational Product Accountability Record” including the following items and maintain it 
with updated information at all times. 
 
investigational drug substance code or product code 
 
receipt date and quantities, and expiry date of investigational drug  
 
lot number 
 
subject identification (subject number) 
 
dispensing log: date and quantity of dispensing and remaining quantity after subject 
dispensing  
 
information to identify the pharmacist who dispenses the investigational drugs  
 
date and quantity of investigational drug returned to the drug management unit, if 
appropriate 
 
record of destruction or loss of unused investigational drug 
 
record of destruction of used investigational drug (empty vial) as needed  

SAP_001.pdf: 
 
 
 
 
Asian Multinational Phase 2 Study of SP-02L (darinaparsin for injection) in 
Patients with Relapsed or Refractory Peripheral T-cell Lymphoma 
 
Protocol Number: SP-02L02 
 
 
 
Statistical Analysis Plan 
 
 
Ver.1.3 
 
 
Solasia Pharma K.K. 
 
 
Approver 
Signature 
Date 
 
 
 
 
 
 
 
 
 


1/18 
SP-02L02_Statistical Analysis Plan_Ver.1.3_20210819 
Table of Contents 
Abbreviations and Terms ............................................................................................................................................. 3 
1 
OVERVIEW ......................................................................................................................................................... 5 
2 
STUDY OBJECTIVES ........................................................................................................................................ 5 
3 
STUDY DESIGN .................................................................................................................................................. 5 
4 
END POINT ......................................................................................................................................................... 5 
5 
ANALYSIS SETS ................................................................................................................................................. 6 
5.1 
Efficacy Analysis Set ...................................................................................................................................... 6 
5.2 
Safety Analysis Set .......................................................................................................................................... 6 
5.3 
PK Analysis Set ............................................................................................................................................... 6 
6 
HANDLING OF SUBJECTS AND DATA ......................................................................................................... 6 
7 
ATTENSION ON ANALYSIS ............................................................................................................................. 7 
7.1 
Data for Statistical Analysis ............................................................................................................................ 7 
7.2 
Descriptive Statistics ....................................................................................................................................... 7 
7.3 
Display Digit ................................................................................................................................................... 7 
7.4 
Changes from the Protocol .............................................................................................................................. 7 
8 
STATISTICAL METHOD .................................................................................................................................. 7 
8.1 
Detail of Statistical Analysis ........................................................................................................................... 7 
8.1.1 Significance Level and Confidence Interval ................................................................................................... 7 
8.2 
Consideration of Statistical Analysis............................................................................................................... 8 
8.2.1 Adjustment by Covariates ............................................................................................................................... 8 
8.2.2 Withdrawal and Missing ................................................................................................................................. 8 
8.2.3 Interim Analysis and Data Monitoring ............................................................................................................ 8 
8.2.4 Multicenter Study ............................................................................................................................................ 8 
8.2.5 Adjustment for Multiplicity ............................................................................................................................ 8 
8.2.6 Integrated Analysis .......................................................................................................................................... 8 
9 
SOFTWARE ......................................................................................................................................................... 8 
10 
SUBJECTS OF THE CLINICAL STUDY ........................................................................................................ 9 
10.1 
Disposition of Patients .................................................................................................................................... 9 
10.1.1 Subject Disposition ......................................................................................................................................... 9 
10.1.2 Analysis Dataset .............................................................................................................................................. 9 
10.1.3 Disposition of Withdrawn Subjects ................................................................................................................. 9 
10.1.4 Demographic and Other Baseline Characteristics ........................................................................................... 9 
10.1.5 Compliance of Study Drug Administration ................................................................................................... 10 
11 
EFFICACY EVALUATION .............................................................................................................................. 11 
11.1 
The Best Overall Response Based on Central Assessment ........................................................................... 11 
11.2 
The Best Overall Response Based on Local Assessment .............................................................................. 11 
11.3 
Comparison of Best Overall Response between Central Assessment and Local Assessment ....................... 11 


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SP-02L02_Statistical Analysis Plan_Ver.1.3_20210819 
11.4 
Other Tabulations for The Best Overall Response ........................................................................................ 11 
11.5 
Percent Change from Baseline of Tumor Size .............................................................................................. 11 
11.6 
Analyses for Survival Time ........................................................................................................................... 11 
12 
SAFETY EVALUATION ................................................................................................................................... 13 
12.1 
Adverse Event ............................................................................................................................................... 13 
12.1.1 Summary of Adverse Events ......................................................................................................................... 13 
12.1.2 Number of Subjects with Any Adverse Event ............................................................................................... 13 
12.1.3 Number of Subjects with Adverse Drug Reaction ........................................................................................ 13 
12.1.4 Number of Subjects with Any Serious Adverse Event .................................................................................. 13 
12.1.5 Number of Subjects with Serious Adverse Drug Reaction ........................................................................... 13 
12.1.6 Number of Subjects with Adverse Event of Special Interest ........................................................................ 14 
12.1.7 Number of Subjects with Any Grouping Adverse Event .............................................................................. 14 
12.1.8 Number of Subjects with Any Grouping Adverse Drug Reaction ................................................................ 15 
12.2 
Laboratory/ECG/Vital sign Parameters Evaluation ...................................................................................... 15 
12.2.1 Summary of Laboratory Parameters ............................................................................................................. 15 
12.2.2 Neurological and Mental Status Assessments ............................................................................................... 15 
12.2.3 Summary of Vital Sign Parameters ............................................................................................................... 15 
12.2.4 Summary of ECG Parameters ....................................................................................................................... 16 
12.2.5 Summary of PK Parameters .......................................................................................................................... 16 
13 
LISTING ............................................................................................................................................................. 17 
 
 
 
 


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Abbreviations and Terms 
List of Abbreviations 
Abbreviation 
Definition 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AITL 
Angioimmunoblastic T-cell Lymphoma 
ALCL 
Anaplastic Large Cell Lymphoma 
BSA 
Body Surface Area 
CI 
Confidence Interval 
CR 
Complete Response 
DCR 
Disease Control Rate 
DOR 
Duration of Response 
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
FAS 
Full Analysis Set 
IPI 
International Prognostic Index  
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events  
ORR 
Overall Response Rate 
OS 
Overall Survival  
PFS 
Progression-Free Survival  
PIT 
Prognostic Index for T-cell lymphoma  
PD 
Progressive Disease 
PK 
Pharmacokinetics 
PKS 
Pharmacokinetics Analysis Set 
PPS 
Per Protocol Set 
PR 
Partial Response 
PTCL 
Peripheral T-cell Lymphoma 
PTCL-NOS 
PTCL-not otherwise specified 
RD 
Relapsed Disease 
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SD 
Stable Disease 
TTR 
Time to Response 
 
 


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List of Terms 
Term 
Definition 
SP-02 
Drug substance code of Darinaparsin 
SP-02L 
Product code of Darinaparsin for injection 
Day 1 
The first day of 5 consecutive days of investigational drug administration in each cycle; 
including the case that the planned dosing on the first day is skipped 
First screening visit 
The day at which the subject signs the informed consent 
Screening period 
The period from the day of the first screening visit to the day before the first day of Cycle 1 
(Day 1 of Cycle 1) 
Treatment period 
The period from the first day of Cycle 1 (Day 1 of Cycle 1) to the day before the first 
examination, observation and investigation scheduled during the follow-up period 
Follow-up period 
The period from the day of the first examination, observation and investigation scheduled 
during the follow-up period to the day of the last examination, observation and investigation 
scheduled during the follow-up period (including follow-up adverse event assessment)  
Study period 
Period consisting of screening period, treatment period and follow-up 
Baseline 
Results at the last time point of examination, observation and investigation before the start of 
the first administration of investigational drug in Cycle 1 
Tumor response 
“Complete Response (CR)” and “Partial Response (PR)” 
Overall Response Rate 
Proportion of subjects with “CR or PR” in the evaluable subject population 
Disease Control Rate 
Proportion of subjects with “CR, PR or Stable Disease (SD)” in the evaluable subject 
population 
Progression-Free 
Survival (PFS) 
Time from the first day of investigational drug administration (Day 1 of Cycle 1) to the date 
of documented "progressive disease" or "relapsed disease", or the date of "death", which 
occurs earlier 
Overall Survival (OS) 
Time from the first day of investigational drug administration (Day 1 of Cycle 1) to the date 
of "death" from any cause 
Time to Response 
(TTR) 
Time from the first day of investigational drug administration (Day 1 of Cycle 1) to the first 
day of tumor response observed for patients who achieved a CR or PR  
Duration of Response 
(DOR) 
Time from the first day of tumor response observed for patients who achieved a CR or PR to 
the date of documented "progressive disease" or "relapsed disease", or the date of "death" 
which occurs earlier 
 
 


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1 
OVERVIEW 
This Statistical Analysis Plan (SAP) specifies details of the statistical analyses to be conducted for the clinical study 
titled “Asian Multinational Phase 2 Study of SP-02L (darinaparsin for injection) in Patients with Relapsed or 
Refractory Peripheral T-cell Lymphoma (PTCL)” (hereafter referred as to “this study”).  
The purpose of the SAP is to describe general or study-specific statistical methodology for this study. Statistical 
results to be reported as an interim report or a final clinical study report (CSR). The SAP would be revised when the 
protocol is revised. It would also be revised if the revision is judged to make the data more credible and useful in 
comparison with the original plan. 
 
 
2 
STUDY OBJECTIVES 
Primary objective 
To evaluate the efficacy of SP-02L monotherapy in patients with relapsed or refractory PTCL 
Secondary objectives 
• 
To evaluate the safety of SP-02L monotherapy in patients with relapsed or refractory PTCL 
• 
To assess the pharmacokinetic (PK) profile of SP-02L at multiple doses in a subgroup of subjects (cf. 
Section 2.6 of protocol) 
 
 
3 
STUDY DESIGN 
This study is a phase 2 multinational, multicenter, single-arm, open-label, non-randomized study conducted in East 
Asia countries/regions. Subjects will receive SP-02L at 300 mg/m2 once daily for 5 consecutive days followed by 
16 days of rest per cycle of 21 day (3 week). SP-02L will be administered for 6 cycles to evaluate the efficacy and 
safety of SP-02L monotherapy using various endpoints. If the subject wishes to continue investigational drug 
administration and the investigator judges that the continuous administration of investigational drug is possible 
and necessary for the subject, the investigational drug administration can be continued beyond 6 cycles. 
Pharmacokinetics will be assessed in subjects enrolled in part or all of the investigational sites in each participating 
country or region at Cycle 1. 
 
 
4 
END POINT 
Primary Endpoint 
Tumor response (best overall response) according to the Revised Response Criteria for Malignant Lymphoma by 
an International Working Group to Standardize Response Criteria for Non-Hodgkin's Lymphomas in 2007 (the 
best overall response up to Cycle 6 based on a central assessment by Efficacy and Safety Review Committee)  
Secondary Endpoints 
 
Progression-Free Survival (PFS) 


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 
Time to Response (TTR) 
 
Duration of Response (DOR) 
 
Overall Survival (OS) 
 
Occurrence of adverse events (AEs) 
 
SP-02L plasma concentration-time profile, PK parameters, and fraction of dose excreted in urine 
 
 
5 
ANALYSIS SETS 
5.1 
Efficacy Analysis Set 
The “full analysis set (FAS)” will consist of subjects who fulfill eligibility criteria (cf. Section 3 of protocol) 
and who take a tumor response assessment (cf. Section 6.14.2 of protocol) at least one time after the 
administration of investigational drug. A group of subjects who have no important protocol deviation 
including violation of eligibility criteria and/or dosage and administration that may affect the efficacy 
evaluation is defined as “per protocol set (PPS)”. FAS will be used for the primary analysis of efficacy 
endpoints, and PPS will be used for the secondary analysis of efficacy endpoints. 
 
5.2 
Safety Analysis Set 
A group of subjects who receive at least one dose of investigational drug is defined as the “safety analysis set 
(SAF)”. SAF will be used for the analysis of all subject characteristics, investigational drug administration and 
safety endpoints. 
 
5.3 
PK Analysis Set 
The “PK analysis set (PKS)” will consist of all subjects who receive at least one dose of investigational drug 
and have at least one point of drug plasma or urine concentration data. PKS will be used for the analysis of PK 
endpoints. 
 
 
6 
HANDLING OF SUBJECTS AND DATA 
Before the data is fixed to be analyzed, the project team will determine the handling of subjects.  
If it is considered that data including laboratory values, 12-lead electrocardiogram (ECG) readings or drug 
plasma/urine concentration measurements has been affected by abnormality of a sample (e.g. hemolysis or milky 
fluid), a technical error, the project team will decide whether or not to exclude that data from analysis prior to the 
data-lock. 
In case that medical judgement is required, the advice from sponsor’s medical experts including a cardiac safety 
advisor will be obtained.  
 
 


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7 
ATTENSION ON ANALYSIS 
7.1 
Data for Statistical Analysis 
Clinical data is collected from medical institution using electronic case report form (eCRF) or is electronically 
transferred from the central laboratory of drug plasma/urine concentration measurement and the central review 
organization of pathology and tumor response. The clinical data collected by eCRF or electronically 
transferred clinical data will be entered into database, cleaned, fixed and then used for statistical analysis. 
Data collection, input, cleaning and fixing are performed under responsibility of a study manager, clinical 
research associates and a data management person in charge. Fixed data is provided by a person in charge of 
data management to that of statistical analysis. 
 
7.2 
Descriptive Statistics 
Following descriptive statistics will be summarized. 
・ Continuous variables 
Number of available data, Mean, Standard deviation (SD), Median, First and third quartile points, 
Minimum and Maximum 
・ Categorical variables 
Frequency and Percentage 
 
7.3 
Display Digit 
・ Mean, SD, median, first and third quartile points, and geometric average will be rounded to one more dps 
than the raw data. 
・ Minimum and Maximum data will be displayed as original decimal point of raw data. 
・ Percentages, Confidence Interval (CI) will be rounded to one decimal point. 
 
7.4 
Changes from the Protocol 
We think that 65 would be more appropriate to consider the age standard of elderly in modern times, so we 
will change the age standard from 61 to 65. 
 
 
8 
STATISTICAL METHOD 
8.1 
Detail of Statistical Analysis 
8.1.1 
Significance Level and Confidence Interval 
Tests with any significance level will not be performed. Confidence Interval will be calculated by 
Clopper-Pearson 'exact' method. 
 


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8.2 
Consideration of Statistical Analysis 
8.2.1 
Adjustment by Covariates 
Adjustment by covariates will not be performed. 
 
8.2.2 
Withdrawal and Missing 
Analyses will be performed with no consideration for withdrawal of subjects. If date of birth is missing, values 
will be complemented as follows. 
・ If day is missing, 15 (middle of the month) will be completed. 
・ If day and month is missing, July 1 (middle of the year) will be completed. 
The others will not be perform any imputation for missing value. 
 
8.2.3 
Interim Analysis and Data Monitoring 
No interim analysis and no early termination for efficacy are planned in this study. 
Interim evaluation for efficacy and safety including PK as needed (cf. Section 8.5.2 of Protocol) will be 
performed at the point when the number of efficacy evaluable subjects reaches 20 and necessary data is 
obtained from these subjects.  
 
8.2.4 
Multicenter Study 
Analyses will be performed with no adjustment for Multicenter. 
 
8.2.5 
Adjustment for Multiplicity 
Analyses will be performed with no adjustment for multiplicity. 
 
8.2.6 
Integrated Analysis 
Not applicable. 
 
 
9 
SOFTWARE 
All analyses will be performed using SAS® Ver9.2 (or later version). 
 
 
 
 


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10 SUBJECTS OF THE CLINICAL STUDY 
10.1 Disposition of Patients 
10.1.1 Subject Disposition 
Numbers of subjects will be counted according to following terms.  
・ Informed consent obtained subjects 
・ Enrolled subjects 
・ Not-enrolled subjects 
・ Treated subjects 
・ Not-treated subjects 
・ Study Completion subjects 
・ Study Withdrawal subjects 
 
10.1.2 Analysis Dataset 
Numbers of subjects will be counted according to following terms. 
・ Efficacy analysis set of FAS 
・ Efficacy analysis set of PPS 
・ SAF 
・ PKS 
 
10.1.3 Disposition of Withdrawn Subjects 
Number of withdrawn subjects will be summarized with reasons for withdrawal.  
 
10.1.4 Demographic and Other Baseline Characteristics 
Descriptive statistics of following variables at screening period will be calculated by ethnic background 
(Japanese, Except Japanese, Korean, Taiwanese, Hong Konger/Chinese and others).  
・ Numerical Variables 
- 
Age (years)  
- 
Sum of the product of the greatest diameter (SPD) of target lesion (major axis and minor axis) (cm2) 
- 
Height (cm)  
- 
Weight (kg)  
- 
Body surface area (BSA) (m2)  
 (BSA (m2) ＝Weight (kg) 0.425×Height (cm) 0.725×0.007184)  
- 
Number of prior medication (chemotherapy or immune therapy) 
 
・ Categorical Variables 
- 
Sex 
- 
Ethnic group/Race 


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- 
Eastern Cooperative Oncology Group (ECOG) Performance Status Scale 
- 
Histopathological classification of lymphoma 
- 
Clinical Symptom Caused by Primary Disease (Concomitant Symptom)  
- 
Clinical stage by Ann Arbor Classification 
- 
International Prognostic Index (IPI) risk group 
- 
Prognosis Index for T-cell lymphoma (PIT) risk group 
- 
Presence of prior medication (chemotherapy or immune therapy) 
- 
Response to most recent therapy 
- 
Presence of prior radiation therapy 
- 
Presence of prior transplant of hematopoietic stem cell transplant 
- 
Other therapy 
- 
Presence of liver enlargement 
- 
Presence of spleen enlargement 
- 
Presence of bone-marrow infiltration 
- 
Presence of Medical History 
- 
Presence of Allergy and/or drug sensitivity 
- 
Neurological and mental status assessments 
 
Presence of finding of cranial nerve abnormalities 
 
Presence of finding of sensory abnormalities 
 
Presence of finding of motor abnormalities 
 
Presence of finding of coordination (gait) abnormalities 
 
Presence of finding of reflex abnormalities 
 
Presence of finding of mental status abnormalities 
- 
Presence of pregnancy 
 
10.1.5 Compliance of Study Drug Administration 
Compliance of SP-02L administration (number of administration completed and skipped) and total volume of 
administration will be summarized by cycle and all cycles in total and by ethnic background (Japanese, Except 
Japanese, Korean, Taiwanese, Hong Konger/Chinese and others). 
 
 


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11 EFFICACY EVALUATION 
11.1 The Best Overall Response Based on Central Assessment 
Based on a central assessment of tumor response by Efficacy and Safety Review Committee, the response up 
to Cycle 6 will be summarized to calculate the overall response rate (ORR), the disease control rate (DCR), 
the best overall response and their 90% Confidence Interval (90% CI) respectively, and count the number of 
subjects per cycle. A binomial test will be performed for the null hypothesis “true objective response rate is 
less than or equal to the threshold objective response rate of 0.1 that is assessed to be ineffective”. 
The same analysis will be performed by histopathological classification (PTCL-not otherwise specified 
[PTCL-NOS], Angioimmunoblastic T-cell Lymphoma [AITL], Anaplastic Large Cell Lymphoma [ALCL] 
ALK-positive and ALCL ALK-negative, other lymphoma), clinical stage according to Ann Arbor 
classification (Stage I, Stage II, Stage III, Stage IV), prognosis risk group according to IPI, prognosis risk 
group based on PIT, response to most recent therapy (Yes (CR/CRu/PR), No (SD/PD), Unknown/Unable to 
assess), ethnic background (Japanese, Except Japanese, Korean, Taiwanese, Hong Konger/Chinese and others), 
sex and age (< 65 years old or ≥ 65 years old). 
 
11.2 The Best Overall Response Based on Local Assessment 
Based on a local assessment of tumor response at each investigational site, the same analysis described in 11.1 
will be performed for the response up to Cycle 6. 
 
11.3 Comparison of Best Overall Response between Central Assessment and Local Assessment 
Based on the central assessment and local assessment of tumor response, cross tabulation will be performed 
for the best overall response up to Cycle 6 in total and by ethnic background (Japanese, Except Japanese, 
Korean, Taiwanese, Hong Konger/Chinese and others).  
 
11.4 Other Tabulations for The Best Overall Response 
Based on a local assessment of tumor response at each investigational site, the same analysis described in 11.1 
will be performed for the response in the entire period. 
To assess the tumor response in each subject, the waterfall plot will be produced to show the rate of tumor 
shrinkage at best overall response based on the central assessment and local assessment of tumor response in 
total and by ethnic background (Japanese, Except Japanese). 
 
11.5 Percent Change from Baseline of Tumor Size 
Based on the central assessment and local assessment of tumor size, the percent change from baseline will be 
plotted using Spider plot. 
 
11.6 Analyses for Survival Time 
PFS, TTR, DOR and OS will be summarized to calculate lower quartile, median, upper quartile and their 90% 


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CI by using Kaplan-Meier method in total and by ethnic background (Japanese, Except Japanese, Korean, 
Taiwanese, Hong Konger/Chinese and others). As for PFS and OS, Kaplan-Meier curve will be displayed. The 
same analysis will be performed by histopathological subtypes (PTCL-NOS, AITL, ALCL ALK-positive, 
ALCL ALK-negative, other lymphoma). 
"Progressive disease (PD)", "Relapsed disease (RD)" or "death" which occurs earlier is defined as 
“progression event”, and “the date of progression” will be identified for analyses of PFS and DOR in 
accordance with the following rules: 
 
The date of judgment of PD or RD based on the local assessment of tumor response by investigator at each 
site (cf. Section 6.14.2 of protocol) is defined as “the date of progression”.  
 
PD or RD includes not only the results of tumor response assessment based on diagnostic imaging data but 
also investigator’s clinical judgment of “Symptomatic Progression” based on clinical symptoms and findings, 
and clinical laboratory test result, etc.). In this case, the date of the judgement is defined as “the date of 
progression”.  
 
If “death” occurs earlier than the judgement of “PD” or “RD”, the date of death is defined as “the date of 
progression”. 
 
If no progression event is confirmed prior to the following events, the most recent date of local assessment of 
tumor response will be defined as “the date of censoring”: 
 
Subsequent therapy for primary disease is initiated 
 
Investigational drug is withdrawn due to adverse drug reaction 
 
Subject is lost to follow up 
 
If a subject is surviving on the date of data cut-off, the most recent date of confirmation of subject’s existence 
is defined as “the date of censoring” for the analysis of OS. For a subject lost to follow-up, the last date when 
the subject’s existence is confirmed prior to the subject’s lost to follow-up is defined as “the date of censoring”. 
If treatment-duration exceeds 2 years, the date after 2 years is defined as “the date of censoring”. 
 
 
 


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12 SAFETY EVALUATION 
Following analyses will be performed on SAF except 12.2.5 and 12.2.5 will be performed on PKS. 
 
12.1 Adverse Event 
12.1.1 Summary of Adverse Events 
Number of subjects with AE will be counted according to following terms in total and by ethnic background 
(Japanese, Except Japanese, Korean, Taiwanese, Hong Konger/Chinese and others).  
・ AE 
・ Serious AE 
・ Adverse drug reaction 
・ Serious Adverse drug reaction 
・ AE leading to withdrawn from the study 
・ Adverse drug reaction leading to withdrawn from the study 
・ AE of NCI-CTCAE Grade 3 or higher 
・ Adverse drug reaction of NCI-CTCAE Grade 3 or higher 
 
12.1.2 Number of Subjects with Any Adverse Event 
The occurrence of AEs will be summarized by system organ class and by preferred term according to the 
Medical Dictionary for Regulatory Activities (MedDRA) dictionary, and by ethnic background (Japanese, 
Except Japanese, Korean, Taiwanese, Hong Konger/Chinese and others) and by severity. 
The bar graph will be produced to show the occurrence of AEs by severity. 
When one subject experiences same PT of AE more than once, the severest event will be counted (National 
Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] Grade 1 < Grade 2 < 
Grade 3 < Grade 4 < Grade 5). Adverse event of NCI-CTCAE Grade 3 or higher will be also summarized in 
the same way. 
 
12.1.3 Number of Subjects with Adverse Drug Reaction 
An adverse drug reaction is defined as an AE with possible relationship with the investigational drug. 
The same analyses described in 12.1.2 will be performed for adverse drug reaction. 
 
12.1.4 Number of Subjects with Any Serious Adverse Event 
The same analyses described in 12.1.2 except graph will be performed for serious AE. 
 
12.1.5 Number of Subjects with Serious Adverse Drug Reaction 
The same analyses described in 12.1.2 except graph will be performed for serious adverse drug reaction. 
 


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12.1.6 Number of Subjects with Adverse Event of Special Interest 
The same analyses described in 12.1.2 except graph will be performed for AESI. AESI is defined AEs that will 
be coded as “Psychiatric disorders”, “Nervous system disorders” or “Hepatobiliary disorders” of system organ 
class according to the MedDRA dictionary. 
 
12.1.7 Number of Subjects with Any Grouping Adverse Event 
The occurrence of AEs will be summarized by any grouping Adverse Event, preferred term according to the 
MedDRA dictionary, and by ethnic background and by severity. Grouping Adverse Event is following. 
 
Grouped Term 
Preferred Terms 
Fatigue/malaise 
Fatigue, Malaise 
Hepatic function test abnormal 
Aspartate aminotransferase increased, Alanine aminotransferase increased, 
Gamma-glutamyltransferase increased 
Anaemia 
Anaemia, Haemoglobin decreased 
Thrombocytopenia 
Thrombocytopenia, Platelet count decreased 
Neutropenia 
Neutropenia, Neutrophil count decreased 
Lymphopenia 
Lymphopenia, Lymphocyte count decreased 
Leukopenia 
Leukopenia, White blood cell count decreased 
Injection site reaction 
Infusion site pain, Injection site pain, Injection site reaction, Injection site 
rash, Infusion site pruritus, Infusion site rash 
Hyperglycaemia 
Hyperglycaemia, Blood glucose increased 
Taste disorder 
Taste disorder, Dysgeusia 
Hyperbilirubinaemia 
Hyperbilirubinaemia, Blood bilirubin increased 
Hypoalbuminaemia 
Hypoalbuminaemia, Blood albumin decreased 
Hypomagnesaemia 
Hypomagnesaemia, Blood magnesium decreased 
Hyponatraemia 
Hyponatraemia, Blood sodium decreased 
Hypokalaemia 
Hypokalaemia, Blood potassium decreased 
Catheter site related reaction 
Catheter site pain, Catheter site related reaction, Catheter site haemorrhage, 
Catheter site erythema, Catheter site bruise, Catheter site pruritus, Catheter 
site rash, Catheter site oedema, Catheter site discharge, Catheter site 
swelling 
Abdominal pain 
Abdominal pain, Abdominal tenderness, Abdominal pain lower, Abdominal 
pain upper 
Sepsis/Bacteraemia 
Sepsis, Bacteraemia, Enterococcal bacteraemia, Escherichia sepsis, 
Pseudomonal sepsis, Device related sepsis, Neutropenic sepsis, 
Staphylococcal bacteraemia 


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Grouped Term 
Preferred Terms 
Neuropathy peripheral 
Neuropathy peripheral, Peripheral sensory neuropathy 
 
 
12.1.8 Number of Subjects with Any Grouping Adverse Drug Reaction 
The same analyses described in 12.1.7 will be performed for Adverse Drug Reaction. 
 
12.2 Laboratory/ECG/Vital sign Parameters Evaluation 
12.2.1 Summary of Laboratory Parameters 
Descriptive statistics of hematologic/biochemical/blood coagulation test parameters specified in the following 
table will be calculated by time point for both of measured values and changes from baseline. 
If laboratory test value is less than or equal to detection limit value, the value is treated as detection limit 
value. 
 
Hematological test 
parameters 
Hemoglobin, Hematocrit, Red blood cell (RBC) count, White blood cell (WBC) 
count, Differential leukocyte count (Band Neutrophils, Segmented Neutrophils, 
Neutrophils, Lymphocyte, Monocyte, Eosinophil, Basophil), Platelet count 
Biochemical test 
parameters 
Sodium (Na), Potassium (K), Chloride (Cl), Calcium (Ca),  
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline 
phosphatase (ALP),  
Lactic dehydrogenase (LDH), Total bilirubin, Total protein, Albumin,  
C-reactive protein (CRP), Creatinine, Blood urea nitrogen, Uric acid, Glucose 
Blood coagulation test 
parameters 
Prothrombin time-INR (PT-INR), Prothrombin time (PT),  
Activated partial thromboplastin time (APTT) 
 
 
12.2.2 Neurological and Mental Status Assessments 
Neurological and mental status will be summarized in shift tables by time point according to following items.  
・ Presence of finding of cranial nerve abnormalities 
・ Presence of finding of sensory abnormalities 
・ Presence of finding of motor abnormalities 
・ Presence of finding of coordination (gait) abnormalities 
・ Presence of finding of reflex abnormalities 
・ Presence of finding of mental status abnormalities 
 
12.2.3 Summary of Vital Sign Parameters 
Descriptive statistics of following vital sign parameters will be calculated by time point for both of measured 


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values and changes from baseline. 
・ Systolic/Diastolic blood pressure (mmHg) 
・ Pulse rate (beats/minute) 
・ Temperature (˚C) 
・ Percutaneous arterial oxygen saturation (SaO2) by a pulse oximeter (%) 
 
 
12.2.4 Summary of ECG Parameters 
Descriptive statistics of following ECG test parameters will be calculated by time point for measured values. 
・ Heart rate (/minute)  
・ RR interval (msec)  
・ QRS interval (msec)  
・ PR interval (msec)  
・ QT interval (msec)  
・ Fridericia corrected QT interval (QTcF) (msec)  
 
12.2.5 Summary of PK Parameters 
Details of calculation of PK parameter and summarization/analyses for concentration and PK parameter are 
described in “Pharmacokinetic analysis plan”. 
 
 


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13 LISTING 
・ Study Completion Status 
・ Withdrawn patients 
・ Study Visit Dates 
・ Demographic and Baseline Information 
・ Primary Disease Diagnosis by Investigators’ and Central Pathology Review 
・ Prior Medication (Chemotherapy or Immune Therapy) 
・ Prior Radiation 
・ Prior Transplants 
・ Other Prior therapy 
・ Medical History 
・ Allergy / Drug Sensitivity 
・ Hepatitis Virus Screening 
・ Study Drug Administration 
・ Tumor Measurements for Target Lesions 
・ Tumor Assessment of Non-Target Lesions 
・ Assessment of Clinical Finding of Lymphoma 
・ Assessment of Tumor Response 
・ Time to Event 
・ Subsequent Therapy 
・ Adverse Events, Sorted by Subject 
・ Adverse Events, Sorted by System Organ Class, Preferred Term and Subject 
・ Serious Adverse Events, Sorted by Subject 
・ Serious Adverse Events, Sorted by System Organ Class, Preferred Term and Subject 
・ Glossary of Adverse Events by System Organ Class 
・ Glossary of Adverse Events by Verbatim Term 
・ Adverse Events, Sorted by Severity, Dose Group, System Organ Class, Preferred Term and Subject 
・ Hematology Laboratory Evaluations 
・ Other Blood Differentiation 
・ Clinical Chemistry Laboratory Evaluations 
・ Coagulation Laboratory Evaluations 
・ Physical Examination 
・ Vital Signs 
・ Concomitant Medications 
・ Concomitant Procedures 
・ Hospitalization 
・ ECG Assessments 


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・ Pharmacokinetic Sample Time and Concentration 
・ PK parameters and fraction of dose excreted 
・ Ratio of peak area and peak area of metabolites 
・ Comments