Brentuximab Vedotin (ADCETRIS) IV Infusion - Special Drug Use Surveillance (All-case Surveillance) "Relapsed or Refractory CD30+ Hodgkin's Lymphoma or Anaplastic Large Cell Lymphoma"
Conditions: Relapsed or Refractory CD30+ Hodgkin's Lymphoma or Anaplastic Large Cell Lymphoma
Sponsor: Takeda

 
 
Title: Special Drug Use Surveillance of Adcetris IV Infusion (All-Case Surveillance) 
"Relapsed or Refractory CD30+ Hodgkin's Lymphoma or Anaplastic Large Cell 
Lymphoma" 
 
NCT Number: NCT02139592 
Protocol Approve Date: 02-Jun-2017 
 
Certain information within this protocol has been redacted (ie, specific content is 
masked irreversibly from view with a black/blue bar) to protect either personally 
identifiable information or company confidential information. 
 
This may include, but is not limited to, redaction of the following: 
 
Named persons or organizations associated with the study. 
 
Patient identifiers within the text, tables, or figures or in by-patient data listings. 
 
Proprietary information, such as scales or coding systems, which are considered 
confidential information under prior agreements with license holder. 
 
Other information as needed to protect confidentiality of Takeda or partners, 
personal information, or to otherwise protect the integrity of the clinical study. 
 
If needed, certain appendices that contain a large volume of personally identifiable 
information or company confidential information may be removed in their entirety if it 
is considered that they do not add substantially to the interpretation of the data (eg, 
appendix of investigator’s curriculum vitae). 
 
Note; This document was translated into English as the language on original version 
was Japanese. 

 
 
 
 
 
Special Drug Use Surveillance Protocol 
Special Drug Use Surveillance of Adcetris IV Infusion 
(All-Case Surveillance) 
“Relapsed or Refractory CD30+ Hodgkin's Lymphoma 
or Anaplastic Large Cell Lymphoma” 
 
 
 
 
 
 
 
 
Version number 
5 
Date of creation 
June 2, 2017 
Sponsor 
Takeda Pharmaceutical Company Limited 
 

 
Table of Contents 
1.0 
Background ..................................................................................................................................... 1 
2.0 
Purpose ............................................................................................................................................ 1 
3.0 
Estimated Enrollment and Its Rationale ...................................................................................... 1 
3.1 
Estimated enrollment ................................................................................................................. 1 
3.2 
Rationale ...................................................................................................................................... 1 
4.0 
Eligible Patients ............................................................................................................................. 1 
5.0 
Dosage Regimen .............................................................................................................................. 2 
6.0 
Expected Study Institutions by Department ................................................................................ 2 
7.0 
Methods ........................................................................................................................................... 2 
7.1 
Observation period ...................................................................................................................... 2 
7.2 
Request for participation in this study and contract with each study institution ................. 2 
7.3 
Method of patient enrollment..................................................................................................... 3 
7.4 
Completion and submission of the case report form ................................................................ 4 
7.5 
Confirmation of all-case surveillance ........................................................................................ 4 
8.0 
Estimated Study Period ................................................................................................................. 4 
9.0 
Outcome Measures ......................................................................................................................... 4 
9.1 
Data to be recorded in Patient Enrollment Form ..................................................................... 5 
9.2 
Data to be recorded in Case Report Form ................................................................................. 5 
 
Cover sheet of Case Report Form ....................................................................................... 5 
9.2.1
 
Patient demographics and baseline characteristics .......................................................... 5 
9.2.2
 
Treatment given ................................................................................................................... 5 
9.2.3
 
Tests and assessments ......................................................................................................... 6 
9.2.4
 
Laboratory tests ............................................................................................................... 6 
9.2.4.1
 
Best response .................................................................................................................... 6 
9.2.4.2
 
Date of the final observation ........................................................................................... 6 
9.2.4.3
 
Other assessments ........................................................................................................... 6 
9.2.4.4
 
Adverse events ..................................................................................................................... 6 
9.2.5
10.0 Data to Be Analyzed and Methods of Analysis ........................................................................... 10 
10.1 Patient disposition .................................................................................................................... 10 
10.2 Patient demographics and baseline characteristics ............................................................... 10 
10.3 Treatment given ........................................................................................................................ 10 
10.4 Safety ......................................................................................................................................... 10 
 
Occurrence of adverse events ............................................................................................ 10 
10.4.1
 
Factors that may affect the safety of Adcetris ................................................................. 11 
10.4.2
 
Changes in laboratory test data over time ...................................................................... 11 
10.4.3
10.5 Efficacy ....................................................................................................................................... 11 
 
Best response ..................................................................................................................... 11 
10.5.1
 
Overall survival ................................................................................................................. 11 
10.5.2
10.6 Interim analyses ....................................................................................................................... 11 

 
11.0 
Posting of Information Regarding This Study ............................................................................ 11 
12.0 Organizational Structure ............................................................................................................. 11 
12.1 Person responsible for administration .................................................................................... 11 
12.2 Proper Use Committee .............................................................................................................. 11 
12.3 Central Enrollment Center ...................................................................................................... 12 
13.0 Contract Research Organization ................................................................................................. 12 
14.0 Other Important Information ...................................................................................................... 12 
14.1 Protocol amendment ................................................................................................................. 12 
14.2 Measures to be taken in response to issues/questions ........................................................... 12 
 
Appendices   
   Appendix 1 Study Schedule................................................................................................................................ 13 
   Appendix 2 Best Response Assessment Criteria................................................................................................. 15 
 

 
1 
1.0 
Background 
There is limited safety information on Adcetris IV Infusion 50 mg (hereinafter referred to as 
Adcetris) collected from Japanese patients in Japanese phase 1/2 studies. It is important to 
promptly collect post-marketing safety information and provide it to healthcare providers. It 
was also deemed that additional surveillance was required to determine the occurrence of 
peripheral nerve disorders, infections, neutropenia, infusion reactions, and pulmonary 
disorders in patients using Adcetris in Japan as post-marketing safety specifications. 
Thus, an all-case surveillance in all patients receiving treatment with Adcetris will be initiated 
as an additional pharmacovigilance activity for Adcetris when the drug is launched. 
This surveillance study will be conducted in compliance with the GPSP Ordinance and other 
related regulatory requirements. 
 
2.0 
Purpose 
The purpose of this study is to evaluate the safety of Adcetris in patients with 
relapsed/refractoryCD30+ Hodgkin's lymphoma or anaplastic large cell lymphoma in the 
routine clinical setting, as well as to collect efficacy information for reference. 
 
3.0 
Estimated Enrollment and Its Rationale 
3.1 Estimated enrollment  
140 patients (with relapsed/refractory CD30+ Hodgkin's lymphoma or anaplastic large cell 
lymphoma) 
 
3.2 Rationale 
It is expected that the detailed evaluation of peripheral nerve disorders, infections, neutropenia, 
infusion reactions, and pulmonary disorders will help better understand the safety profile of 
Adcetris in the routine clinical setting, which will lead to the assessment of the risk-benefit 
balance of the drug. 
The frequencies of peripheral nerve disorders, infections, neutropenia (≥Grade 3), infusion 
reaction, and pulmonary disorder in non-Japanese phase 2 studies (pooled study data from a 
study in patients with Hodgkin's lymphoma [SG035-0003, 102 patients] and a study in 
patients with systemic anaplastic large cell lymphoma [SG035-0004, 58 patients]) were 56%, 
61%, 20%, 11%, and 6%, respectively. 
Observation of infusion reactions with the lowest frequency of ≥10 patients, aside from 
pulmonary disorders, with a probability of 95% would require 140 patients, which was 
therefore determined to be the estimated enrollment. It is estimated that when the number of 
patients enrolled reaches 140 patients, ≥4 patients have adverse events of pulmonary disorder 
with a probability of 95%. 
 
4.0 
Eligible Patients 
All patients receiving treatment with Adcetris 

 
2 
 
5.0 
Dosage Regimen 
The usual adult dosage is 1.8 mg/kg (body weight) of brentuximab vedotin (recombinant) 
infused intravenously once every three weeks. The dose should be adjusted depending on the 
patient's condition. 
See the "PRECAUTIONS" section of the package insert. 
 
6.0 
Expected Study Institutions by Department 
The study will be conducted at all institutions using Adcetris (e.g., department of hematology) 
(approximately 100 study institutions are expected to participate in the study). 
 
7.0 
Methods 
7.1 Observation period 
From the start of treatment with Adcetris until the completion of 16 cycles [3 weeks per cycle] 
 
* Rationale for the selection of the observation period 
The assessment of the treatment cycle with the initial onset of adverse events in a clinical 
study [SGN35-006, the extended treatment group] evaluating the safety of Adcetris after Cycle 
17 showed a tendency that most adverse events occurred before Cycle 16. In addition, the 
types and severities did not differ between adverse events occurring after Cycle 17 and those 
occurring before Cycle 16. This suggested that the safety profile of Adcetris would be 
generally determined before Cycle 16. Therefore, the observation period was defined as the 
period from the start of treatment with Adcetris until the completion of 16 cycles. 
 
7.2 Request for participation in this study and contract with each study institution 
Paper-based case report forms will be used. To ask each study institution to participate in the 
study, the representative of Takeda Pharmaceutical Company Limited (representative of 
Takeda) will confirm before supply of Adcetris and the start of the study that each study 
institution meets all requirements for study institutions and investigators specified below, and 
have a written contract with the study institution after prior explanation of the study provided 
before supply of Adcetris. 
 
(1) Requirements for each study institution and investigator 
1) Requirements for each study institution 
[1] Is able to cooperate with this all-case surveillance and have a contract with the 
sponsor. 
[2] Is able to provide specialized treatment for hematopoietic tumors. 
[3] Is able to provide emergency treatment if required (including a case where such a 
treatment can be provided in conjunction with another institution 
). 

 
3 
* When emergency treatment is provided in conjunction with another institution, 
information on Adcetris safety measures and treatment of adverse drug reactions should 
be shared between the institution and the other institution to build a coalition. 
 
2) Requirements for each investigator 
[1] Has adequate knowledge and experience regarding the treatment of hematopoietic 
tumors, or is under the direction of a healthcare professional having such knowledge 
and experience. 
[2] Is able to cooperate with this all-case surveillance. 
 
 
(2) Prior explanation of the study to be provided before supply of Adcetris and the request for 
participation in this study 
Using “Request for Participation in the Special Drug Use Surveillance,” “Study Outline,” 
“Patient Enrollment Form (sample),” “Case Report Form Parts 1 and 2 (sample),” 
“Precautions for Use/Instruction Manual,” and “Proper Usage Guide,” the representative of 
Takeda will explain the purpose and methods (e.g., all-case surveillance) of this survey study 
and information regarding the proper use of Adcetris to the investigator and ask him/her to 
participate in the all-case surveillance. 
The representative of Takeda will also confirm with the investigator that the institution and 
the investigator meet all requirements. 
 
(3) Request for participation in this study and contract with each study institution 
The representative of Takeda will have a written contract with the study institution after 
obtaining their agreement to participate in this study Takeda Pharmaceutical Company 
Limited will inform the outsourced Adcetris supplier that the contract is concluded and 
Adcetris should be supplied to the study institution. The representative of Takeda will deliver 
patient enrollment forms to the investigator. 
 
7.3 Method of patient enrollment 
The central enrollment method via FAX will be used. For each patient scheduled to receive 
treatment with Adcetris after the date of the start of the term of the contract with the study 
institution, the investigator will complete patient enrollment by submitting the Patient 
Enrollment Form with information required for patient enrollment filled in (see Section 9.1) 
via FAX to the Central Enrollment Center (see Section 12.3) until noon of the day before the 
date of the expected initial dose of Adcetris. 
The Central Enrollment Center will review the Patient Enrollment Form and send the 
Enrollment Completion Notice to the investigator via FAX. After receiving the Enrollment 
Completion Notice, the investigator will initiate treatment with Adcetris. 
 

 
4 
The Case Report Form consists of Parts 1 and 2 per patient. 
The representative of Takeda will deliver Case Report Form Part 1, which is issued after 
enrollment confirmation by the Central Enrollment Center, to the investigator. Case Report 
Form Part 2 is issued after Takeda Pharmaceutical receives Case Report Form Part 1. 
 
7.4 Completion and submission of the case report form 
For all patients requiring the completion of the case report form, the investigator will complete 
the case report form during the period from the start of treatment with Adcetris until the end of 
Cycle 4 and within 1 month after the end of Cycle 16, and submit it to the representative of 
Takeda. 
If treatment with Adcetris is discontinued for any reason before the end of the observation 
period, the investigator will complete the case report form within 1 month after the completion 
of required observation submit it to the representative of Takeda. If treatment with Adcetris is 
discontinued due to any adverse event, however, the investigator will continue to observe the 
patient after treatment discontinuation until the adverse event resolves or improves wherever 
possible, and then complete the case report form and submit it to the representative of Takeda. 
 
7.5 Confirmation of all-case surveillance 
After the completion of the study, the principal investigator will confirm that case report forms 
of all patients treated with Adcetris have been submitted, and sign or fill in his/her name with 
seal on All-Case Surveillance Confirmation Form and submit it to the representative of 
Takeda. 
 
8.0 
Estimated Study Period 
Study period: Starts on the day of the launch of Adcetris (April, 2014) and ends once the 
all-case surveillance is no longer a condition for approval of the product. 
Patient enrollment period: Starts on the day of the launch of Adcetris (April, 2014) and ends 
once the all-case surveillance is no longer a condition for approval of the 
product. 
 
The expected number of enrolled patients (140) was achieved. Therefore, the study will move 
to the period only requiring patient enrollment (not requiring the completion and submission 
of case report forms). 
After moving to the period only requiring patient enrollment, it may be required to complete 
and submit case report forms upon request by the regulatory authority. 
 
9.0 
Outcome Measures 
The investigator will record data listed below in both Patient Enrollment and Case Report 
Forms. Study schedule is provided in in Appendix 1. 

 
5 
9.1 Data to be recorded in Patient Enrollment Form 
1) Outcome measures 
Name of the institution, name of the investigator completing Patient Enrollment Form, 
expected date of the start of treatment with Adcetris, patient identification number, patient 
initial, sex, date of birth, diagnosis, performance status, CD30, past history of severe 
hypersensitivity to any ingredient of Adcetris, expected concomitant use of other 
antineoplastic drugs, and presence/absence of infections, peripheral nerve disorders, hepatic 
disorders, severe renal disorders, or pregnancy/breast-feeding 
2) When to collect outcome measure data 
At the time of patient enrollment 
 
9.2 Data to be recorded in Case Report Form 
 Cover sheet of Case Report Form 
9.2.1
Date of the finial completion of Case Report Form and name of the investigator completing 
Case Report Form 
 
 Patient demographics and baseline characteristics 
9.2.2
1) Outcome measures 
Date of diagnosis of Hodgkin's or anaplastic large cell lymphoma, site of involvement, 
ALK (in patients with anaplastic large cell lymphoma), clinical stage, presence/absence of 
B symptoms, ECOG Performance Status, therapeutic category, (presence/absence and 
detail of) hypersensitivity disposition, viral test results, past history of and concurrent 
pulmonary disorders, past history of and concurrent malignant tumours, (presence/absence 
and detail of) concurrent illnesses [other than pulmonary disorders and malignant tumours], 
(presence/absence and detail of) past history[other than pulmonary disorders and malignant 
tumours], height, weight, smoking history, and (presence/absence and detail of) prior 
treatment for Hodgkin's lymphoma or anaplastic large cell lymphoma (including drug 
therapy, radiotherapy, and hematopoietic stem cell transplantation) 
2) When to collect outcome measure data 
At the start of treatment with Adcetris 
 
 Treatment given 
9.2.3
1) Outcome measures 
Treatment with Adcetris and premedication to prevent infusion reaction (dose, date of 
premedication, and reasons for premedication to prevent infusion reaction and its 
discontinuation), (use or non-use, type, and date of) post-baseline hematopoietic stem cell 
transplantation, (presence/absence, name, and duration of) drugs other than Adcetris used 
for the treatment of the primary disease, and (presence/absence, name, and duration of) 
drugs used for the prevention of infection 
2) When to collect outcome measure data 

 
6 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Tests and assessments 
9.2.4
 Laboratory tests 
9.2.4.1
1) Outcome measures 
Red blood cell count, hemoglobin level, white blood cell count, neutrophil count, 
lymphocyte count, platelet count, total bilirubin, AST, ALT, LDH, BUN, and serum 
creatinine 
2) When to collect outcome measure data 
At each test time point during the period from the start of treatment with Adcetris until the 
completion of 16 cycles (or upon discontinuation of treatment with Adcetris) 
 
 Best response 
9.2.4.2
1) Outcome measures 
The best response (CR, CRu [for patients with no PET scan data], PR, SD, or PD) will be 
assessed based on CT and PET scans of the neck, chest, abdomen, and pelvis according to 
the best response assessment criteria (see Appendix). 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Date of the final observation 
9.2.4.3
1) Outcome measures 
Date of the final observation 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Other assessments 
9.2.4.4
1) Outcome measures 
Pregnancy during the observation period (for females only) 
If pregnancy is detected during the observation period, it should be reported to the 
representative of Takeda immediately. 
2) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Adverse events 
9.2.5
1) Outcome measures 

 
7 
Presence/absence of adverse events (see Table 1), adverse event terms, date of onset, 
CTCAE grade (the worst one), seriousness and its reason (see Table 2), (presence/absence 
and detail of) action taken to Adcetris, (presence/absence and detail of) intervention for 
adverse events, date of outcome, outcome, causal relationship with Adcetris* (see Table 3), 
and changes in laboratory test values associated with adverse events over time 
If the outcome is “not recovered/not resolved” or “unknown,” and the causal relationship 
with Adcetris is considered unevaluable, the event should be followed wherever possible. 
* If the event is considered not related to Adcetris, its rationale should be collected. If the causal 
relationship with Adcetris is considered unevaluable, its reason should be collected. 
Note) Points to consider regarding adverse events 
Worsening of the primary disease should not be regarded as an adverse event. However, abnormal 
worsening of the primary disease (e.g., worsening beyond the expected natural course of the 
disease) should be regarded as an adverse event. 
Disease progression should be regarded as worsening of the primary disease rather than an adverse 
event. However, clinical or laboratory progression of an existing cancer (including new metastasis) 
that meets any of the criteria for the seriousness of adverse events (see Table 2) should be 
considered a serious adverse event. 
2) Adverse events of particular interest 
The events listed below are events of particular interest; detailed information on these 
events should be collected wherever possible it they are observed:  
• Peripheral nerve disorders 
• Infections 
• Neutropenia 
• Infusion reactions 
• Pulmonary disorders 
 
* Rationale for the selection of adverse events of particular interest 
Of important identified risks listed in Risk Management Plan, those listed above were 
selected as adverse events of particular interest based on the following rationales: 
a) Peripheral nerve disorders 
Peripheral nerve disorders are frequently observed after treatment with Adcetris. If the 
event of peripheral nerve disorder becomes severe, it is difficult to continue treatment 
with Adcetris. It is important to control the onset of the event to allow for continuation of 
treatment (including dose reduction and restart of treatment after treatment interruption). 
Therefore, the profile of peripheral nerve disorders in Japanese patients as an adverse 
event of particular interest will be determined (i.e., information useful for continuation of 
treatment with Adcetris, including risk factors, commonly reported time to onset, 
outcomes, and the status of treatment with Adcetris, will be collected). 
b) Infections 

 
8 
It is expected that Adcetris is used in patients who are immunocompromised due to prior 
treatment or the prior disease or those who are complicated with infection, and the 
incidence of infections is likely to be high. Therefore, the profile of infections in Japanese 
patients as an adverse event of particular interest (i.e., the incidence and temporal 
relationship with the onset of neutropenia/lymphopenia) will be determined. 
c) Neutropenia 
It is expected that Adcetris is used in patients with decreased neutrophil count due to prior 
treatment, which may increase the risk of infection and result in a high incidence of 
infection/severe infection. It is important to control the neutrophil count to allow for 
continuation of treatment (including dose reduction and restart of treatment after 
treatment interruption) in terms of the prevention of infection. Therefore, the profile of 
neutropenia in Japanese patients as an adverse event of particular interest will be 
determined (i.e., the status of treatment with Adcetris and neutrophil count control will be 
assessed and information useful for continuation of treatment with Adcetris will be 
collected). 
d) Infusion reactions  
Infusion reactions are characteristic of monoclonal antibody preparations, the profile of 
infusion reactions in Japanese patients as an adverse event of particular interest (including 
the status of premedication and the percentage of patients using premedication to prevent 
infusion reactions [use/non-use of premedication to prevent infusion reactions]) will be 
determined. 
e) Pulmonary disorders 
The occurrence of pulmonary disorders in Japanese patients receiving monotherapy with 
Adcetris as an adverse event of particular interest will be determined. 
3) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 

 
9 
Table 1 Definition of an Adverse Event 
An adverse event (AE) is any untoward or undesirable medical occurrence in a patient linked in time 
with the use of a pharmaceutical/ medicinal product and which does not necessarily have to have a 
causal relationship with this treatment or may or may not be considered related to the product. 
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not related to the medicinal product. 
Adverse events also include: 
•Symptoms observed in an infant breast-fed by a mother receiving treatment with Adcetris. 
 
Table 2 Criteria for the Seriousness of Adverse Events 
An adverse event meeting any of the following criteria will be considered serious: 
1. Results in death. 
2. Is life-threatening. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization. 
4. Results in persistent or significant disability/incapacity. 
5. Is a congenital anomaly/birth defect. 
6. Is a medically important condition due to any of the above 1 to 5, including those listed in “Takeda 
Medically Significant AE List.” 
 
Takeda Medically Significant AE List 
•Acute respiratory failure/acute respiratory distress 
syndrome (ARDS) 
•Anaphylactic shock 
•Torsade de pointes/ventricular fibrillation/ventricular 
tachycardia 
•Acute kidney failure 
•Malignant hypertension                 
•Pulmonary hypertension 
•Convulsive seizure (including convulsion and 
epilepsy) 
•Pulmonary fibrosis (including interstitial 
pneumonia) 
•Agranulocytosis 
•Neuroleptic malignant syndrome/malignant 
hyperthermia 
•Aplastic anemia 
•Spontaneous abortion/stillbirth and fetal 
death 
•Toxic epidermal necrolysis/oculomucocutaneous 
syndrome (Stevens-Johnson syndrome) 
 •(Suspected) transmission of infection via a 
drug 
•Hepatic necrosis 
•(Suspected) endotoxic shock 
•Acute hepatic failure                    
 
 

 
10 
Table 3 Criteria for the Assessment of Causal Relationship between Adverse Events and 
Adcetris 
Causality 
Assessment criterion 
Related 
There is a temporal relationship between the event and Adcetris (and 
the clinical course after treatment discontinuation). Or, there are other 
contributing factors, such as the primary disease, concurrent illnesses, 
and concomitant medications/therapies, but it is also likely that the 
event is attributable to Adcetris. 
Not related 
There is no temporal relationship between the event and Adcetris. Or, 
it is very likely that the event is attributable to other factors, such as 
the primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
Indeterminate 
There is limited information required for the assessment of causal 
relationship, such as temporal relationship between the event and 
Adcetris (and the clinical course after treatment discontinuation), the 
primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
 
10.0 
Data to Be Analyzed and Methods of Analysis 
10.1 Patient disposition 
Data to be analyzed includes the number of enrolled patients, the number of patients whose 
case report forms are available, and the number of patients included in and excluded from the 
safety/efficacy analysis set and reasons for inclusion/exclusion. 
 
10.2 Patient demographics and baseline characteristics 
Data to be analyzed includes sex, age, disease duration, site of involvement, and clinical stage. 
 
10.3 Treatment given 
Data to be analyzed includes the status of treatment with Adcetris and concomitant 
medications. 
 
10.4 Safety 
The measures specified below will be analyzed using the safety analysis set. Adverse events 
will be coded using MedDRA/J and summarized using (Preferred Terms [PTs]) and System 
Organ Classes [SOCs]). 
 Occurrence of adverse events 
10.4.1
The frequency of adverse events observed during the observation period will be analyzed 
by type, time of onset, seriousness, and Adcetris. 
 

 
11 
 Factors that may affect the safety of Adcetris 
10.4.2
The frequency of adverse events observed during the observation period will be analyzed 
by patient background factors (sex, age, presence/absence of concurrent renal disorders, 
and presence/absence of concurrent hepatic disorders) and treatment given (the status of 
treatment with Adcetris and concomitant medications). 
 
 Changes in laboratory test data over time 
10.4.3
Summary statistics of laboratory test values at baseline and post-baseline will be calculated. 
 
10.5 Efficacy 
The measures specified below will be analyzed using the efficacy analysis set. 
 Best response 
10.5.1
The best response after 16 cycles of treatment with Adcetris (or upon discontinuation of 
treatment with Adcetris) will be analyzed. 
 
 Overall survival 
10.5.2
The time to death (regardless of the cause of death) will be analyzed using the “final 
observation date” in specified in Section 9.2.4.3 as the date of survival confirmation and the 
date of outcome of an adverse event with “Died/fetal” recorded in the Outcome field 
specified in Section 9.2.5 as the date of death 
 
10.6 Interim analyses 
For patients whose case report forms are collected through November 30, 2014 with evaluable 
safety evaluation, analyses similar to the ones described in Sections 10.1 to 10.4 will be 
performed to evaluate and analyze safety information obtained in this study at an early stage 
and publish them as appropriate. 
 
11.0 
Posting of Information Regarding This Study 
Prior to the start of the study, Takeda Pharmaceutical Company Limited will register 
information regarding this study to the public website specified below. 
 
Japan Pharmaceutical Information Center-Clinical Trials Information 
 
ClinicalTrials.gov (a clinical trial registration system provided by the National Institutes of Health) 
 
12.0 
Organizational Structure 
12.1 Person responsible for administration 
, Takeda Pharmaceutical Company Limited 
 
12.2 Proper Use Committee 
The committee will provide advice on the protocol, data analysis, publication of study results, 
promotion of the proper use of Adcetris, and safety measures. 
PPD

 
12 
(Listed in the order of the Japanese syllabary) 
 
12.3 Central Enrollment Center 
 
 
13.0 
Contract Research Organization 
 
14.0 
Other Important Information 
14.1 Protocol amendment 
During the study, the sponsor will monitor the occurrence of adverse drug reactions and 
serious adverse drug reactions that cannot be predicted by the progress of the study and 
precautions for use, the presence/absence of an increase in the frequency of specific adverse 
drug reactions, and the appropriateness of outcome measures, and review and amend this 
protocol as appropriate. If the approval of partial changes to “Dosage and Administration” or 
“Indication” is obtained during the study, the sponsor will consider the necessity of 
amendment of this protocol as appropriate, and amend the protocol as appropriate. 
 
14.2 Measures to be taken in response to issues/questions 
If any safety and/or efficacy issue is detected, the sponsor will examine data closely and 
consider what measures should be taken. 
 
 
 
PPD
PPD
PPD

 
13 
         Time point 
 
 
   Procedure 
Observation period 
At the time of 
patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Patient enrollment 
Date of the expected initial dose of Adcetris 
○ 
 
 
 
 
Patient identification number 
○ 
Patient initial 
○ 
 
Sex 
○ 
Date of birth 
○ 
Diagnosis 
○ 
Performance status 
○ 
 
 
 
CD30 
○ 
 
 
 
Past history of severe hypersensitivity to any 
ingredient of Adcetris 
○ 
 
 
 
Expected concomitant use of other 
antineoplastic drugs 
○ 
 
 
 
Presence/absence of infections 
○ 
 
 
 
 
Presence/absence of peripheral nerve 
disorders 
○ 
 
 
 
Presence/absence of hepatic disorders 
○ 
 
 
 
Presence/absence of severe renal disorders 
○ 
 
 
 
Presence/absence of pregnancy/breast-feeding 
○ 
 
 
 
Patient demographics and baseline characteristics 
Date of diagnosis of Hodgkin or anaplastic 
large-cell lymphoma 
○ 
 
 
Site of involvement 
○ 
 
 
ALK (in patients with anaplastic large cell 
lymphoma) 
○ 
 
 
Clinical stage 
○ 
 
 
Presence/absence of B symptoms 
○ 
 
 
ECOG Performance Status 
 
○ 
 
 
 
Therapeutic category 
 
○ 
 
 
Hypersensitivity disposition 
 
○ 
 
 
Viral test results 
 
○ 
 
 
Past history of and concurrent pulmonary 
disorders 
 
○ 
 
 
Past history of and concurrent malignant 
tumours 
 
○ 
 
 
Concurrent illness (other than pulmonary 
disorders and malignant tumours) 
 
○ 
 
 
Past history (other than pulmonary disorders 
and malignant tumours) 
 
○ 
 
 
 
Height and weight 
 
○ 
 
 
Smoking history 
 
○ 
 
 
Prior treatment for Hodgkin's or anaplastic 
large cell lymphoma 
 
○ 
 
 
 
Appendix 1 Study Schedule 

 
14 
 
 
         Time point 
 
 
   Procedure 
Observation period 
At the time of 
patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Treatment given 
Treatment with Adcetris 
 
○ 
○ 
 
 
Post-baseline hematopoietic stem cell 
transplantation 
 
○ 
○ 
Drug(s) other than Adcetris used for the 
treatment of the primary disease 
 
○ 
○ 
Drug(s) used for the prevention of infection 
 
○ 
○ 
Tests and assessments 
Laboratory tests (red blood cell count, 
hemoglobin level, white blood cell count, 
neutrophil count, lymphocyte count, platelet 
count, and liver and kidney function tests) 
 
 
○ 
○ 
Best response 
 
 
○ 
○ 
Date of the final observation 
 
 
 
○ 
○ 
Presence/absence of pregnancy (for females 
only) 
 
○ 
○ 
Adverse events 
 
○ 
○ 
   ○   : Data collected 
   ○   : Data collected throughout the period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
15 
Appendix 2 Best Response Assessment Criteria (Revised Response Criteria for Malignant Lymphoma*)  
* Extracted from “General Rules for the Clinical and Pathological Studies on Tumors of Hematopoietic and 
Lymphoid Tissues, March 2000 [First Edition]) 
For patients with PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
 The patient is PET negative. If the patient is PET negative, any residual tumor on CT does not matter. 
1)-2Variably FDG-avid lymphoma 
 The patient did not undergo PET before treatment. If the patient was negative before treatment, the patient 
must meet all the following criteria: 
 [1] All nodal target lesions are normal. 
 [2] All extranodal target lesions have resolved. 
 [3] All nodal non-target lesions are normal. 
 [4] The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
 [5] All extranodal non-target lesions have resolved. 
2) A patient with bone marrow infiltration at baseline must be negative for bone marrow infiltration. A patient 
with no bone marrow infiltration at baseline should be regarded as “negative” because bone marrow test is 
not required. 
3) The patient has no new lesion. 
PR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
If the patient had one or more PET positive lesions, or was PET negative AND had bone marrow infiltration 
at baseline, the patient must be positive for bone marrow infiltration at the time of restaging (or have not 
undergone testing). 
1)-2Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
3) All nodal non-target lesions are normal or free from enlargement. 
4) All extranodal non-target lesions have resolved or free from enlargement. 
5) Bone marrow infiltration does not matter. Testing is not required. 
6) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR but meets any of the criteria 1 and 2 to 6 and 7 listed below, the 
patient will be assessed as having progressive disease (PD). If the patient meets any of the criteria listed below 
after being assessed as achieving CR, the patient will be assessed as having a relapsed disease (RD): 
1)-1 Routinely FDG-avid lymphoma 
 The patient has one or more PET positive lesions. 
1)-2 Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
3) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 

 
16 
diameter) or re-enlargement. 
4) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
5) The long diameter of the nodal target lesion which was once normalized and assessed as CR exceeded 1.5 
cm. The extranodal target lesion which once resolved reappeared. 
6) The patient has a new lesion. 
7) The patient became positive after being once negative for bone marrow infiltration. 
 
 
For patients with no PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
5) All extranodal non-target lesions have resolved. 
6) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
7) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
8) A patient with bone marrow infiltration or indeterminate at baseline must be negative for bone marrow 
infiltration. 
 A patient with no bone marrow infiltration at baseline should be regarded as “negative” because bone 
marrow test is not required. 
9) The patient has no new lesion. 
CRu   
The patient had bone marrow infiltration or was indeterminate at baseline AND meets all the following 
criteria: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) All extranodal non-target lesions have resolved. 
5) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
6) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
7) The patient is indeterminate for bone marrow infiltration. 
8) The patient has no new lesion. 
 
OR 
1) The patient has a 75% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal. 
3) All extranodal non-target lesions have resolved. 
4) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
5) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
6) The patient has no bone marrow infiltration or indeterminate. 

 
17 
7) The patient has no new lesion. 
PR 
The patient meets all the above criteria for CRu except for criterion 6. A patient with bone marrow infiltration 
or indeterminate at baseline must be positive for bone marrow infiltration at the time of restaging. 
Or, the patient meets all the following criteria: 
1) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal or free from enlargement. 
3) All extranodal non-target lesions have resolved or free from enlargement. 
4) Enlarged liver, spleen, and kidneys have resolved or are free from progression. 
5) All tumor-related symptom (fever and night sweat) have resolved. AND abnormal tumor-related laboratory 
test results (tumor-related increase in LDH) became normal. 
6) Bone marrow infiltration does not matter. Testing is not required. 
7) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR or CRu but meets any of the criteria below, the patient will be 
assessed as having progressive disease (PD). If the patient meets any of the criteria listed below after being 
assessed as achieving CR or CRu, the patient will be assessed as having a relapsed disease (RD): 
1) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
2) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 
diameter) or re-enlargement. 
3) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
4) The extranodal target lesion which once resolved and was assesses as CR or CRu reappeared. 
5) Obvious progression or recurrence of enlarged liver, spleen, or kidney. 
6) Obvious progression or recurrence of tumor-related subjective and objective symptoms (fever and night 
sweat) or abnormal tumor-related laboratory test results (tumor-related increase in LDH). 
7) The patient became positive after being once negative for bone marrow infiltration. 
8) The patient has a new lesion. 
 

 
 
 
 
 
Special Drug Use Surveillance Protocol 
Special Drug Use Surveillance of Adcetris IV Infusion 
(All-Case Surveillance) 
“Relapsed or Refractory CD30+ Hodgkin's Lymphoma 
or Anaplastic Large Cell Lymphoma” 
 
 
 
 
 
 
 
 
Version number 
4 
Date of creation 
September 6, 2016 
Sponsor 
Takeda Pharmaceutical Company Limited 
 

 
Table of Contents 
1.0 
Background ..................................................................................................................................... 1 
2.0 
Purpose ............................................................................................................................................ 1 
3.0 
Estimated Enrollment and Its Rationale ...................................................................................... 1 
3.1 
Estimated enrollment ................................................................................................................. 1 
3.2 
Rationale ...................................................................................................................................... 1 
4.0 
Eligible Patients ............................................................................................................................. 1 
5.0 
Dosage Regimen .............................................................................................................................. 2 
6.0 
Expected Study Institutions by Department ................................................................................ 2 
7.0 
Methods ........................................................................................................................................... 2 
7.1 
Observation period ...................................................................................................................... 2 
7.2 
Request for participation in this study and contract with each study institution ................. 2 
7.3 
Method of patient enrollment..................................................................................................... 3 
7.4 
Completion and submission of the case report form ................................................................ 4 
7.5 
Confirmation of all-case surveillance ........................................................................................ 4 
8.0 
Estimated Study Period ................................................................................................................. 4 
9.0 
Outcome Measures ......................................................................................................................... 4 
9.1 
Data to be recorded in Patient Enrollment Form ..................................................................... 5 
9.2 
Data to be recorded in Case Report Form ................................................................................. 5 
 
Cover sheet of Case Report Form ....................................................................................... 5 
9.2.1
 
Patient demographics and baseline characteristics .......................................................... 5 
9.2.2
 
Treatment given ................................................................................................................... 5 
9.2.3
 
Tests and assessments ......................................................................................................... 6 
9.2.4
 
Laboratory tests ............................................................................................................... 6 
9.2.4.1
 
Best response .................................................................................................................... 6 
9.2.4.2
 
Date of the final observation ........................................................................................... 6 
9.2.4.3
 
Other assessments ........................................................................................................... 6 
9.2.4.4
 
Adverse events ..................................................................................................................... 6 
9.2.5
10.0 Data to Be Analyzed and Methods of Analysis ........................................................................... 10 
10.1 Patient disposition .................................................................................................................... 10 
10.2 Patient demographics and baseline characteristics ............................................................... 10 
10.3 Treatment given ........................................................................................................................ 10 
10.4 Safety ......................................................................................................................................... 10 
 
Occurrence of adverse events ............................................................................................ 10 
10.4.1
 
Factors that may affect the safety of Adcetris ................................................................. 11 
10.4.2
 
Changes in laboratory test data over time ...................................................................... 11 
10.4.3
10.5 Efficacy ....................................................................................................................................... 11 
 
Best response ..................................................................................................................... 11 
10.5.1
 
Overall survival ................................................................................................................. 11 
10.5.2
10.6 Interim analyses ....................................................................................................................... 11 

 
11.0 
Posting of Information Regarding This Study ............................................................................ 11 
12.0 Organizational Structure ............................................................................................................. 11 
12.1 Person responsible for administration .................................................................................... 11 
12.2 Proper Use Committee .............................................................................................................. 11 
12.3 Central Enrollment Center ...................................................................................................... 12 
13.0 Contract Research Organization ................................................................................................. 12 
14.0 Other Important Information ...................................................................................................... 12 
14.1 Protocol amendment ................................................................................................................. 12 
14.2 Measures to be taken in response to issues/questions ........................................................... 12 
 
Appendices  
   Appendix 1 Study Schedule................................................................................................................................ 13 
   Appendix 2 Best Response Assessment Criteria................................................................................................. 15 
 

 
1 
1.0 
Background 
There is limited safety information on Adcetris IV Infusion 50 mg (hereinafter referred to as 
Adcetris) collected from Japanese patients in Japanese phase 1/2 studies. It is important to 
promptly collect post-marketing safety information and provide it to healthcare providers. It 
was also deemed that additional surveillance was required to determine the occurrence of 
peripheral nerve disorders, infections, neutropenia, infusion reactions, and pulmonary 
disorders in patients using Adcetris in Japan as post-marketing safety specifications. 
Thus, an all-case surveillance in all patients receiving treatment with Adcetris will be initiated 
as an additional pharmacovigilance activity for Adcetris when the drug is launched. 
This surveillance study will be conducted in compliance with the GPSP Ordinance and other 
related regulatory requirements. 
 
2.0 
Purpose 
The purpose of this study is to evaluate the safety of Adcetris in patients with 
relapsed/refractoryCD30+ Hodgkin's lymphoma or anaplastic large cell lymphoma in the 
routine clinical setting, as well as to collect efficacy information for reference. 
 
3.0 
Estimated Enrollment and Its Rationale 
3.1 Estimated enrollment  
140 patients (with relapsed/refractory CD30+ Hodgkin's lymphoma or anaplastic large cell 
lymphoma) 
 
3.2 Rationale 
It is expected that the detailed evaluation of peripheral nerve disorders, infections, neutropenia, 
infusion reactions, and pulmonary disorders will help better understand the safety profile of 
Adcetris in the routine clinical setting, which will lead to the assessment of the risk-benefit 
balance of the drug. 
The frequencies of peripheral nerve disorders, infections, neutropenia (≥Grade 3), infusion 
reaction, and pulmonary disorder in non-Japanese phase 2 studies (pooled study data from a 
study in patients with Hodgkin's lymphoma [SG035-0003, 102 patients] and a study in 
patients with systemic anaplastic large cell lymphoma [SG035-0004, 58 patients]) were 56%, 
61%, 20%, 11%, and 6%, respectively. 
Observation of infusion reactions with the lowest frequency of ≥10 patients, aside from 
pulmonary disorders, with a probability of 95% would require 140 patients, which was 
therefore determined to be the estimated enrollment. It is estimated that when the number of 
patients enrolled reaches 140 patients, ≥4 patients have adverse events of pulmonary disorder 
with a probability of 95%. 
 
4.0 
Eligible Patients 
All patients receiving treatment with Adcetris 

 
2 
 
5.0 
Dosage Regimen 
The usual adult dosage is 1.8 mg/kg (body weight) of brentuximab vedotin (recombinant) 
infused intravenously once every three weeks. The dose should be adjusted depending on the 
patient's condition. 
See the "PRECAUTIONS" section of the package insert. 
 
6.0 
Expected Study Institutions by Department 
The study will be conducted at all institutions using Adcetris (e.g., department of hematology) 
(approximately 100 study institutions are expected to participate in the study). 
 
7.0 
Methods 
7.1 Observation period 
From the start of treatment with Adcetris until the completion of 16 cycles [3 weeks per cycle] 
 
* Rationale for the selection of the observation period 
The assessment of the treatment cycle with the initial onset of adverse events in a clinical 
study [SGN35-006, the extended treatment group] evaluating the safety of Adcetris after Cycle 
17 showed a tendency that most adverse events occurred before Cycle 16. In addition, the 
types and severities did not differ between adverse events occurring after Cycle 17 and those 
occurring before Cycle 16. This suggested that the safety profile of Adcetris would be 
generally determined before Cycle 16. Therefore, the observation period was defined as the 
period from the start of treatment with Adcetris until the completion of 16 cycles. 
 
7.2 Request for participation in this study and contract with each study institution 
Paper-based case report forms will be used. To ask each study institution to participate in the 
study, the representative of Takeda Pharmaceutical Company Limited (representative of 
Takeda) will confirm before supply of Adcetris and the start of the study that each study 
institution meets all requirements for study institutions and investigators specified below, and 
have a written contract with the study institution after prior explanation of the study provided 
before supply of Adcetris. 
 
(1) Requirements for each study institution and investigator 
1) Requirements for each study institution 
[1] Is able to cooperate with this all-case surveillance and have a contract with the 
sponsor. 
[2] Is able to provide specialized treatment for hematopoietic tumors. 
[3] Is able to provide emergency treatment if required (including a case where such a 
treatment can be provided in conjunction with another institution 
). 

 
3 
* When emergency treatment is provided in conjunction with another institution, 
information on Adcetris safety measures and treatment of adverse drug reactions should 
be shared between the institution and the other institution to build a coalition. 
 
2) Requirements for each investigator 
[1] Has adequate knowledge and experience regarding the treatment of hematopoietic 
tumors, or is under the direction of a healthcare professional having such knowledge 
and experience. 
[2] Is able to cooperate with this all-case surveillance. 
 
 
(2) Prior explanation of the study to be provided before supply of Adcetris and the request for 
participation in this study 
Using “Request for Participation in the Special Drug Use Surveillance,” “Study Outline,” 
“Patient Enrollment Form (sample),” “Case Report Form Parts 1 and 2 (sample),” 
“Precautions for Use/Instruction Manual,” and “Proper Usage Guide,” the representative of 
Takeda will explain the purpose and methods (e.g., all-case surveillance) of this survey study 
and information regarding the proper use of Adcetris to the investigator and ask him/her to 
participate in the all-case surveillance. 
The representative of Takeda will also confirm with the investigator that the institution and 
the investigator meet all requirements. 
 
(3) Request for participation in this study and contract with each study institution 
The representative of Takeda will have a written contract with the study institution after 
obtaining their agreement to participate in this study Takeda Pharmaceutical Company 
Limited will inform the outsourced Adcetris supplier that the contract is concluded and 
Adcetris should be supplied to the study institution. The representative of Takeda will deliver 
patient enrollment forms to the investigator. 
 
7.3 Method of patient enrollment 
The central enrollment method via FAX will be used. For each patient scheduled to receive 
treatment with Adcetris after the date of the start of the term of the contract with the study 
institution, the investigator will complete patient enrollment by submitting the Patient 
Enrollment Form with information required for patient enrollment filled in (see Section 9.1) 
via FAX to the Central Enrollment Center (see Section 12.3) until noon of the day before the 
date of the expected initial dose of Adcetris. 
The Central Enrollment Center will review the Patient Enrollment Form and send the 
Enrollment Completion Notice to the investigator via FAX. After receiving the Enrollment 
Completion Notice, the investigator will initiate treatment with Adcetris. 
 

 
4 
The Case Report Form consists of Parts 1 and 2 per patient. 
The representative of Takeda will deliver Case Report Form Part 1, which is issued after 
enrollment confirmation by the Central Enrollment Center, to the investigator. Case Report 
Form Part 2 is issued after Takeda Pharmaceutical receives Case Report Form Part 1. 
 
7.4 Completion and submission of the case report form 
For all patients requiring the completion of the case report form, the investigator will complete 
the case report form during the period from the start of treatment with Adcetris until the end of 
Cycle 4 and within 1 month after the end of Cycle 16, and submit it to the representative of 
Takeda. 
If treatment with Adcetris is discontinued for any reason before the end of the observation 
period, the investigator will complete the case report form within 1 month after the completion 
of required observation submit it to the representative of Takeda. If treatment with Adcetris is 
discontinued due to any adverse event, however, the investigator will continue to observe the 
patient after treatment discontinuation until the adverse event resolves or improves wherever 
possible, and then complete the case report form and submit it to the representative of Takeda. 
 
7.5 Confirmation of all-case surveillance 
After the completion of the study, the principal investigator will confirm that case report forms 
of all patients treated with Adcetris have been submitted, and sign or fill in his/her name with 
seal on All-Case Surveillance Confirmation Form and submit it to the representative of 
Takeda. 
 
8.0 
Estimated Study Period 
Study period: Starts on the day of the launch of Adcetris (April, 2014) and ends once the 
all-case surveillance is no longer a condition for approval of the product. 
Patient enrollment period: Starts on the day of the launch of Adcetris (April, 2014) and ends 
once the all-case surveillance is no longer a condition for approval of the 
product. 
 
The expected number of enrolled patients (140) was achieved. Therefore, the study will move 
to the period only requiring patient enrollment (not requiring the completion and submission 
of case report forms). 
After moving to the period only requiring patient enrollment, it may be required to complete 
and submit case report forms upon request by the regulatory authority. 
 
9.0 
Outcome Measures 
The investigator will record data listed below in both Patient Enrollment and Case Report 
Forms. Study schedule is provided in in Appendix 1. 

 
5 
9.1 Data to be recorded in Patient Enrollment Form 
1) Outcome measures 
Name of the institution, name of the investigator completing Patient Enrollment Form, 
expected date of the start of treatment with Adcetris, patient identification number, patient 
initial, sex, date of birth, diagnosis, performance status, CD30, past history of severe 
hypersensitivity to any ingredient of Adcetris, expected concomitant use of other 
antineoplastic drugs, and presence/absence of infections, peripheral nerve disorders, hepatic 
disorders, severe renal disorders, or pregnancy/breast-feeding 
2) When to collect outcome measure data 
At the time of patient enrollment 
 
9.2 Data to be recorded in Case Report Form 
 Cover sheet of Case Report Form 
9.2.1
Date of the finial completion of Case Report Form and name of the investigator completing 
Case Report Form 
 
 Patient demographics and baseline characteristics 
9.2.2
1) Outcome measures 
Date of diagnosis of Hodgkin's or anaplastic large cell lymphoma, site of involvement, 
ALK (in patients with anaplastic large cell lymphoma), clinical stage, presence/absence of 
B symptoms, ECOG Performance Status, therapeutic category, (presence/absence and 
detail of) hypersensitivity disposition, viral test results, past history of and concurrent 
pulmonary disorders, past history of and concurrent malignant tumours, (presence/absence 
and detail of) concurrent illnesses [other than pulmonary disorders and malignant tumours], 
(presence/absence and detail of) past history[other than pulmonary disorders and malignant 
tumours], height, weight, smoking history, and (presence/absence and detail of) prior 
treatment for Hodgkin's lymphoma or anaplastic large cell lymphoma (including drug 
therapy, radiotherapy, and hematopoietic stem cell transplantation) 
2) When to collect outcome measure data 
At the start of treatment with Adcetris 
 
 Treatment given 
9.2.3
1) Outcome measures 
Treatment with Adcetris and premedication to prevent infusion reaction (dose, date of 
premedication, and reasons for premedication to prevent infusion reaction and its 
discontinuation), (use or non-use, type, and date of) post-baseline hematopoietic stem cell 
transplantation, (presence/absence, name, and duration of) drugs other than Adcetris used 
for the treatment of the primary disease, and (presence/absence, name, and duration of) 
drugs used for the prevention of infection 
2) When to collect outcome measure data 

 
6 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Tests and assessments 
9.2.4
 Laboratory tests 
9.2.4.1
1) Outcome measures 
Red blood cell count, hemoglobin level, white blood cell count, neutrophil count, 
lymphocyte count, platelet count, total bilirubin, AST, ALT, LDH, BUN, and serum 
creatinine 
2) When to collect outcome measure data 
At each test time point during the period from the start of treatment with Adcetris until the 
completion of 16 cycles (or upon discontinuation of treatment with Adcetris) 
 
 Best response 
9.2.4.2
1) Outcome measures 
The best response (CR, CRu [for patients with no PET scan data], PR, SD, or PD) will be 
assessed based on CT and PET scans of the neck, chest, abdomen, and pelvis according to 
the best response assessment criteria (see Appendix). 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Date of the final observation 
9.2.4.3
1) Outcome measures 
Date of the final observation 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Other assessments 
9.2.4.4
1) Outcome measures 
Pregnancy during the observation period (for females only) 
If pregnancy is detected during the observation period, it should be reported to the 
representative of Takeda immediately. 
2) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Adverse events 
9.2.5
1) Outcome measures 

 
7 
Presence/absence of adverse events (see Table 1), adverse event terms, date of onset, 
CTCAE grade (the worst one), seriousness and its reason (see Table 2), (presence/absence 
and detail of) action taken to Adcetris, (presence/absence and detail of) intervention for 
adverse events, date of outcome, outcome, causal relationship with Adcetris* (see Table 3), 
and changes in laboratory test values associated with adverse events over time 
If the outcome is “not recovered/not resolved” or “unknown,” and the causal relationship 
with Adcetris is considered unevaluable, the event should be followed wherever possible. 
* If the event is considered not related to Adcetris, its rationale should be collected. If the causal 
relationship with Adcetris is considered unevaluable, its reason should be collected. 
Note) Points to consider regarding adverse events 
Worsening of the primary disease should not be regarded as an adverse event. However, abnormal 
worsening of the primary disease (e.g., worsening beyond the expected natural course of the 
disease) should be regarded as an adverse event. 
Disease progression should be regarded as worsening of the primary disease rather than an adverse 
event. However, clinical or laboratory progression of an existing cancer (including new metastasis) 
that meets any of the criteria for the seriousness of adverse events (see Table 2) should be 
considered a serious adverse event. 
2) Adverse events of particular interest 
The events listed below are events of particular interest; detailed information on these 
events should be collected wherever possible it they are observed:  
• Peripheral nerve disorders 
• Infections 
• Neutropenia 
• Infusion reactions 
• Pulmonary disorders 
 
* Rationale for the selection of adverse events of particular interest 
Of important identified risks listed in Risk Management Plan, those listed above were 
selected as adverse events of particular interest based on the following rationales: 
a) Peripheral nerve disorders 
Peripheral nerve disorders are frequently observed after treatment with Adcetris. If the 
event of peripheral nerve disorder becomes severe, it is difficult to continue treatment 
with Adcetris. It is important to control the onset of the event to allow for continuation of 
treatment (including dose reduction and restart of treatment after treatment interruption). 
Therefore, the profile of peripheral nerve disorders in Japanese patients as an adverse 
event of particular interest will be determined (i.e., information useful for continuation of 
treatment with Adcetris, including risk factors, commonly reported time to onset, 
outcomes, and the status of treatment with Adcetris, will be collected). 
b) Infections 

 
8 
It is expected that Adcetris is used in patients who are immunocompromised due to prior 
treatment or the prior disease or those who are complicated with infection, and the 
incidence of infections is likely to be high. Therefore, the profile of infections in Japanese 
patients as an adverse event of particular interest (i.e., the incidence and temporal 
relationship with the onset of neutropenia/lymphopenia) will be determined. 
c) Neutropenia 
It is expected that Adcetris is used in patients with decreased neutrophil count due to prior 
treatment, which may increase the risk of infection and result in a high incidence of 
infection/severe infection. It is important to control the neutrophil count to allow for 
continuation of treatment (including dose reduction and restart of treatment after 
treatment interruption) in terms of the prevention of infection. Therefore, the profile of 
neutropenia in Japanese patients as an adverse event of particular interest will be 
determined (i.e., the status of treatment with Adcetris and neutrophil count control will be 
assessed and information useful for continuation of treatment with Adcetris will be 
collected). 
d) Infusion reactions  
Infusion reactions are characteristic of monoclonal antibody preparations, the profile of 
infusion reactions in Japanese patients as an adverse event of particular interest (including 
the status of premedication and the percentage of patients using premedication to prevent 
infusion reactions [use/non-use of premedication to prevent infusion reactions]) will be 
determined. 
e) Pulmonary disorders 
The occurrence of pulmonary disorders in Japanese patients receiving monotherapy with 
Adcetris as an adverse event of particular interest will be determined. 
3) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 

 
9 
Table 1 Definition of an Adverse Event 
An adverse event (AE) is any untoward or undesirable medical occurrence in a patient linked in time 
with the use of a pharmaceutical/ medicinal product and which does not necessarily have to have a 
causal relationship with this treatment or may or may not be considered related to the product. 
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not related to the medicinal product. 
Adverse events also include: 
• Symptoms observed in an infant breast-fed by a mother receiving treatment with Adcetris. 
 
Table 2 Criteria for the Seriousness of Adverse Events 
An adverse event meeting any of the following criteria will be considered serious: 
1. Results in death. 
2. Is life-threatening. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization. 
4. Results in persistent or significant disability/incapacity. 
5. Is a congenital anomaly/birth defect. 
6. Is a medically important condition due to any of the above 1 to 5, including those listed in “Takeda 
Medically Significant AE List.” 
 
Takeda Medically Significant AE List 
• Acute respiratory failure/acute respiratory distress 
syndrome (ARDS) 
• Anaphylactic shock 
• Torsade de pointes/ventricular 
fibrillation/ventricular tachycardia 
• Acute kidney failure 
• Malignant hypertension                 
• Pulmonary hypertension 
• Convulsive seizure (including convulsion and 
epilepsy) 
• Pulmonary fibrosis (including interstitial 
pneumonia) 
• Agranulocytosis 
• Neuroleptic malignant syndrome/malignant 
hyperthermia 
• Aplastic anemia 
• Spontaneous abortion/stillbirth and fetal death 
• Toxic epidermal necrolysis/oculomucocutaneous 
syndrome (Stevens-Johnson syndrome) 
• (Suspected) transmission of infection via a 
drug 
• Hepatic necrosis 
• (Suspected) endotoxic shock 
• Acute hepatic failure                    
 
 

 
10 
Table 3 Criteria for the Assessment of Causal Relationship between Adverse Events and 
Adcetris 
Causality 
Assessment criterion 
Related 
There is a temporal relationship between the event and Adcetris (and 
the clinical course after treatment discontinuation). Or, there are other 
contributing factors, such as the primary disease, concurrent illnesses, 
and concomitant medications/therapies, but it is also likely that the 
event is attributable to Adcetris. 
Not related 
There is no temporal relationship between the event and Adcetris. Or, 
it is very likely that the event is attributable to other factors, such as 
the primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
Indeterminate 
There is limited information required for the assessment of causal 
relationship, such as temporal relationship between the event and 
Adcetris (and the clinical course after treatment discontinuation), the 
primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
 
10.0 
Data to Be Analyzed and Methods of Analysis 
10.1 Patient disposition 
Data to be analyzed includes the number of enrolled patients, the number of patients whose 
case report forms are available, and the number of patients included in and excluded from the 
safety/efficacy analysis set and reasons for inclusion/exclusion. 
 
10.2 Patient demographics and baseline characteristics 
Data to be analyzed includes sex, age, disease duration, site of involvement, and clinical stage. 
 
10.3 Treatment given 
Data to be analyzed includes the status of treatment with Adcetris and concomitant 
medications. 
 
10.4 Safety 
The measures specified below will be analyzed using the safety analysis set. Adverse events 
will be coded using MedDRA/J and summarized using (Preferred Terms [PTs]) and System 
Organ Classes [SOCs]). 
 Occurrence of adverse events 
10.4.1
The frequency of adverse events observed during the observation period will be analyzed 
by type, time of onset, seriousness, and Adcetris. 
 

 
11 
 Factors that may affect the safety of Adcetris 
10.4.2
The frequency of adverse events observed during the observation period will be analyzed 
by patient background factors (sex, age, presence/absence of concurrent renal disorders, 
and presence/absence of concurrent hepatic disorders) and treatment given (the status of 
treatment with Adcetris and concomitant medications). 
 
 Changes in laboratory test data over time 
10.4.3
Summary statistics of laboratory test values at baseline and post-baseline will be calculated. 
 
10.5 Efficacy 
The measures specified below will be analyzed using the efficacy analysis set. 
 Best response 
10.5.1
The best response after 16 cycles of treatment with Adcetris (or upon discontinuation of 
treatment with Adcetris) will be analyzed. 
 
 Overall survival 
10.5.2
The time to death (regardless of the cause of death) will be analyzed using the “final 
observation date” in specified in Section 9.2.4.3 as the date of survival confirmation and the 
date of outcome of an adverse event with “Died/fetal” recorded in the Outcome field 
specified in Section 9.2.5 as the date of death 
 
10.6 Interim analyses 
For patients whose case report forms are collected through November 30, 2014 with evaluable 
safety evaluation, analyses similar to the ones described in Sections 10.1 to 10.4 will be 
performed to evaluate and analyze safety information obtained in this study at an early stage 
and publish them as appropriate. 
 
11.0 
Posting of Information Regarding This Study 
Prior to the start of the study, Takeda Pharmaceutical Company Limited will register 
information regarding this study to the public website specified below. 
 
Japan Pharmaceutical Information Center-Clinical Trials Information 
 
ClinicalTrials.gov (a clinical trial registration system provided by the National Institutes of Health) 
 
12.0 
Organizational Structure 
12.1 Person responsible for administration 
, Takeda Pharmaceutical Company Limited 
 
12.2 Proper Use Committee 
The committee will provide advice on the protocol, data analysis, publication of study results, 
promotion of the proper use of Adcetris, and safety measures. 
PPD

 
12 
(Listed in the order of the Japanese syllabary) 
 
12.3 Central Enrollment Center 
 
 
13.0 
Contract Research Organization 
 
14.0 
Other Important Information 
14.1 Protocol amendment 
During the study, the sponsor will monitor the occurrence of adverse drug reactions and 
serious adverse drug reactions that cannot be predicted by the progress of the study and 
precautions for use, the presence/absence of an increase in the frequency of specific adverse 
drug reactions, and the appropriateness of outcome measures, and review and amend this 
protocol as appropriate. If the approval of partial changes to “Dosage and Administration” or 
“Indication” is obtained during the study, the sponsor will consider the necessity of 
amendment of this protocol as appropriate, and amend the protocol as appropriate. 
 
14.2 Measures to be taken in response to issues/questions 
If any safety and/or efficacy issue is detected, the sponsor will examine data closely and 
consider what measures should be taken. 
 
 
 
PPD
PPD
PPD

 
13 
         Time point 
 
 
   Procedure 
Observation period 
At the time of 
patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Patient enrollment 
Date of the expected initial dose of Adcetris 
○ 
 
 
 
 
Patient identification number 
○ 
Patient initial 
○ 
 
Sex 
○ 
Date of birth 
○ 
Diagnosis 
○ 
Performance status 
○ 
 
 
 
CD30 
○ 
 
 
 
Past history of severe hypersensitivity to any 
ingredient of Adcetris 
○ 
 
 
 
Expected concomitant use of other 
antineoplastic drugs 
○ 
 
 
 
Presence/absence of infections 
○ 
 
 
 
 
Presence/absence of peripheral nerve 
disorders 
○ 
 
 
 
Presence/absence of hepatic disorders 
○ 
 
 
 
Presence/absence of severe renal disorders 
○ 
 
 
 
Presence/absence of pregnancy/breast-feeding 
○ 
 
 
 
Patient demographics and baseline characteristics 
Date of diagnosis of Hodgkin or anaplastic 
large-cell lymphoma 
○ 
 
 
Site of involvement 
○ 
 
 
ALK (in patients with anaplastic large cell 
lymphoma) 
○ 
 
 
Clinical stage 
○ 
 
 
Presence/absence of B symptoms 
○ 
 
 
ECOG Performance Status 
 
○ 
 
 
 
Therapeutic category 
 
○ 
 
 
Hypersensitivity disposition 
 
○ 
 
 
Viral test results 
 
○ 
 
 
Past history of and concurrent pulmonary 
disorders 
 
○ 
 
 
Past history of and concurrent malignant 
tumours 
 
○ 
 
 
Concurrent illness (other than pulmonary 
disorders and malignant tumours) 
 
○ 
 
 
Past history (other than pulmonary disorders 
and malignant tumours) 
 
○ 
 
 
 
Height and weight 
 
○ 
 
 
Smoking history 
 
○ 
 
 
Prior treatment for Hodgkin's or anaplastic 
large cell lymphoma 
 
○ 
 
 
 
Appendix 1 Study Schedule 

 
14 
 
 
         Time point 
 
 
   Procedure 
Observation period 
At the time of 
patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Treatment given 
Treatment with Adcetris 
 
○ 
○ 
 
 
Post-baseline hematopoietic stem cell 
transplantation 
 
○ 
○ 
Drug(s) other than Adcetris used for the 
treatment of the primary disease 
 
○ 
○ 
Drug(s) used for the prevention of infection 
 
○ 
○ 
Tests and assessments 
Laboratory tests (red blood cell count, 
hemoglobin level, white blood cell count, 
neutrophil count, lymphocyte count, platelet 
count, and liver and kidney function tests) 
 
 
○ 
○ 
Best response 
 
 
○ 
○ 
Date of the final observation 
 
 
 
○ 
○ 
Presence/absence of pregnancy (for females 
only) 
 
○ 
○ 
Adverse events 
 
○ 
○ 
   ○   : Data collected 
   ○   : Data collected throughout the period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
15 
Appendix 2 Best Response Assessment Criteria (Revised Response Criteria for Malignant Lymphoma*)  
* Extracted from “General Rules for the Clinical and Pathological Studies on Tumors of Hematopoietic and 
Lymphoid Tissues, March 2000 [First Edition]) 
For patients with PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
 The patient is PET negative. If the patient is PET negative, any residual tumor on CT does not matter. 
1)-2Variably FDG-avid lymphoma 
 The patient did not undergo PET before treatment. If the patient was negative before treatment, the patient 
must meet all the following criteria: 
 [1] All nodal target lesions are normal. 
 [2] All extranodal target lesions have resolved. 
 [3] All nodal non-target lesions are normal. 
 [4] The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
 [5] All extranodal non-target lesions have resolved. 
2) A patient with bone marrow infiltration at baseline must be negative for bone marrow infiltration. A patient 
with no bone marrow infiltration at baseline should be regarded as “negative” because bone marrow test is 
not required. 
3) The patient has no new lesion. 
PR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
If the patient had one or more PET positive lesions, or was PET negative AND had bone marrow infiltration 
at baseline, the patient must be positive for bone marrow infiltration at the time of restaging (or have not 
undergone testing). 
1)-2Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
3) All nodal non-target lesions are normal or free from enlargement. 
4) All extranodal non-target lesions have resolved or free from enlargement. 
5) Bone marrow infiltration does not matter. Testing is not required. 
6) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR but meets any of the criteria 1 and 2 to 6 and 7 listed below, the 
patient will be assessed as having progressive disease (PD). If the patient meets any of the criteria listed below 
after being assessed as achieving CR, the patient will be assessed as having a relapsed disease (RD): 
1)-1 Routinely FDG-avid lymphoma 
 The patient has one or more PET positive lesions. 
1)-2 Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
3) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 

 
16 
diameter) or re-enlargement. 
4) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
5) The long diameter of the nodal target lesion which was once normalized and assessed as CR exceeded 1.5 
cm. The extranodal target lesion which once resolved reappeared. 
6) The patient has a new lesion. 
7) The patient became positive after being once negative for bone marrow infiltration. 
 
 
For patients with no PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
5) All extranodal non-target lesions have resolved. 
6) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
7) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
8) A patient with bone marrow infiltration or indeterminate at baseline must be negative for bone marrow 
infiltration. 
 A patient with no bone marrow infiltration at baseline should be regarded as “negative” because bone 
marrow test is not required. 
9) The patient has no new lesion. 
CRu   
The patient had bone marrow infiltration or was indeterminate at baseline AND meets all the following 
criteria: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) All extranodal non-target lesions have resolved. 
5) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
6) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
7) The patient is indeterminate for bone marrow infiltration. 
8) The patient has no new lesion. 
 
OR 
1) The patient has a 75% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal. 
3) All extranodal non-target lesions have resolved. 
4) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
5) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
6) The patient has no bone marrow infiltration or indeterminate. 

 
17 
7) The patient has no new lesion. 
PR 
The patient meets all the above criteria for CRu except for criterion 6. A patient with bone marrow infiltration 
or indeterminate at baseline must be positive for bone marrow infiltration at the time of restaging. 
Or, the patient meets all the following criteria: 
1) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal or free from enlargement. 
3) All extranodal non-target lesions have resolved or free from enlargement. 
4) Enlarged liver, spleen, and kidneys have resolved or are free from progression. 
5) All tumor-related symptom (fever and night sweat) have resolved. AND abnormal tumor-related laboratory 
test results (tumor-related increase in LDH) became normal. 
6) Bone marrow infiltration does not matter. Testing is not required. 
7) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR or CRu but meets any of the criteria below, the patient will be 
assessed as having progressive disease (PD). If the patient meets any of the criteria listed below after being 
assessed as achieving CR or CRu, the patient will be assessed as having a relapsed disease (RD): 
1) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
2) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 
diameter) or re-enlargement. 
3) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
4) The extranodal target lesion which once resolved and was assesses as CR or CRu reappeared. 
5) Obvious progression or recurrence of enlarged liver, spleen, or kidney. 
6) Obvious progression or recurrence of tumor-related subjective and objective symptoms (fever and night 
sweat) or abnormal tumor-related laboratory test results (tumor-related increase in LDH). 
7) The patient became positive after being once negative for bone marrow infiltration. 
8) The patient has a new lesion. 
 

 
 
 
 
 
Special Drug Use Surveillance Protocol 
Special Drug Use Surveillance of Adcetris IV Infusion 
(All-Case Surveillance) 
“Relapsed or Refractory CD30+ Hodgkin's Lymphoma 
or Anaplastic Large Cell Lymphoma” 
 
 
 
 
 
 
 
 
Version number 
3 
Date of creation 
April 1, 2015 
Sponsor 
Takeda Pharmaceutical Company Limited 
 

 
Table of Contents 
1.0 
Background .................................................................................................................................................... 1 
2.0 
Purpose ........................................................................................................................................................... 1 
3.0 
Estimated Enrollment and Its Rationale ......................................................................................................... 1 
3.1 
Estimated enrollment .................................................................................................................................. 1 
3.2 
Rationale..................................................................................................................................................... 1 
4.0 
Eligible Patients.............................................................................................................................................. 1 
5.0 
Dosage Regimen ............................................................................................................................................ 2 
6.0 
Expected Study Institutions by Department ................................................................................................... 2 
7.0 
Methods .......................................................................................................................................................... 2 
7.1 
Observation period ..................................................................................................................................... 2 
7.2 
Request for participation in this study and contract with each study institution ........................................ 2 
7.3 
Method of patient enrollment ..................................................................................................................... 3 
7.4 
Completion and submission of the case report form .................................................................................. 4 
7.5 
Confirmation of all-case surveillance ......................................................................................................... 4 
8.0 
Estimated Study Period .................................................................................................................................. 4 
9.0 
Outcome Measures ......................................................................................................................................... 4 
9.1 
Data to be recorded in Patient Enrollment Form ........................................................................................ 5 
9.2 
Data to be recorded in Case Report Form .................................................................................................. 5 
 
Cover sheet of Case Report Form ...................................................................................................... 5 
9.2.1
 
Patient demographics and baseline characteristics ............................................................................. 5 
9.2.2
 
Treatment given .................................................................................................................................. 5 
9.2.3
 
Tests and assessments ......................................................................................................................... 6 
9.2.4
 
Laboratory tests .............................................................................................................................. 6 
9.2.4.1
 
Best response .................................................................................................................................. 6 
9.2.4.2
 
Date of the final observation .......................................................................................................... 6 
9.2.4.3
 
Other assessments........................................................................................................................... 6 
9.2.4.4
 
Adverse events ................................................................................................................................... 6 
9.2.5
10.0 
Data to Be Analyzed and Methods of Analysis ............................................................................................ 10 
10.1 
Patient disposition .................................................................................................................................... 10 
10.2 
Patient demographics and baseline characteristics ................................................................................... 10 
10.3 
Treatment given ........................................................................................................................................ 10 
10.4 
Safety ........................................................................................................................................................ 10 
 
Occurrence of adverse events ........................................................................................................... 10 
10.4.1
 
Factors that may affect the safety of Adcetris .................................................................................. 11 
10.4.2
 
Changes in laboratory test data over time ........................................................................................ 11 
10.4.3
10.5 
Efficacy .................................................................................................................................................... 11 
 
Best response) .................................................................................................................................. 11 
10.5.1
 
Overall survival ................................................................................................................................ 11 
10.5.2
10.6 
Interim analyses ........................................................................................................................................ 11 

 
11.0 
Posting of Information Regarding This Study .............................................................................................. 11 
12.0 
Organizational Structure ............................................................................................................................... 11 
12.1 
Person responsible for administration ...................................................................................................... 11 
12.2 
Proper Use Committee ............................................................................................................................. 11 
12.3 
Central Enrollment Center ........................................................................................................................ 12 
13.0 
Contract Research Organization ................................................................................................................... 12 
14.0 
Other Important Information ........................................................................................................................ 12 
14.1 
Protocol amendment ................................................................................................................................. 12 
14.2 
Measures to be taken in response to issues/questions .............................................................................. 12 
 
Appendices  
   Appendix 1 Study Schedule................................................................................................................................ 13 
   Appendix 2 Best Response Assessment Criteria................................................................................................. 15 
 

 
1 
1.0 
Background 
There is limited safety information on Adcetris IV Infusion 50 mg (hereinafter referred to as 
Adcetris) collected from Japanese patients in Japanese phase 1/2 studies. It is important to 
promptly collect post-marketing safety information and provide it to healthcare providers. It 
was also deemed that additional surveillance was required to determine the occurrence of 
peripheral nerve disorders, infections, neutropenia, infusion reactions, and pulmonary 
disorders in patients using Adcetris in Japan as post-marketing safety specifications. 
Thus, an all-case surveillance in all patients receiving treatment with Adcetris will be initiated 
as an additional pharmacovigilance activity for Adcetris when the drug is launched. 
This surveillance study will be conducted in compliance with the GPSP Ordinance and other 
related regulatory requirements. 
 
2.0 
Purpose 
The purpose of this study is to evaluate the safety of Adcetris in patients with 
relapsed/refractoryCD30+ Hodgkin's lymphoma or anaplastic large cell lymphoma in the 
routine clinical setting, as well as to collect efficacy information for reference. 
 
3.0 
Estimated Enrollment and Its Rationale 
3.1 Estimated enrollment  
140 patients (with relapsed/refractory CD30+ Hodgkin's lymphoma or anaplastic large cell 
lymphoma) 
 
3.2 Rationale 
It is expected that the detailed evaluation of peripheral nerve disorders, infections, neutropenia, 
infusion reactions, and pulmonary disorders will help better understand the safety profile of 
Adcetris in the routine clinical setting, which will lead to the assessment of the risk-benefit 
balance of the drug. 
The frequencies of peripheral nerve disorders, infections, neutropenia (≥Grade 3), infusion 
reaction, and pulmonary disorder in non-Japanese phase 2 studies (pooled study data from a 
study in patients with Hodgkin's lymphoma [SG035-0003, 102 patients] and a study in 
patients with systemic anaplastic large cell lymphoma [SG035-0004, 58 patients]) were 56%, 
61%, 20%, 11%, and 6%, respectively. 
Observation of infusion reactions with the lowest frequency of ≥10 patients, aside from 
pulmonary disorders, with a probability of 95% would require 140 patients, which was 
therefore determined to be the estimated enrollment. It is estimated that when the number of 
patients enrolled reaches 140 patients, ≥4 patients have adverse events of pulmonary disorder 
with a probability of 95%. 
 
4.0 
Eligible Patients 
All patients receiving treatment with Adcetris 

 
2 
 
5.0 
Dosage Regimen 
The usual adult dosage is 1.8 mg/kg (body weight) of brentuximab vedotin (recombinant) 
infused intravenously once every three weeks. The dose should be adjusted depending on the 
patient's condition. 
See the "PRECAUTIONS" section of the package insert. 
 
6.0 
Expected Study Institutions by Department 
The study will be conducted at all institutions using Adcetris (e.g., department of hematology) 
(approximately 100 study institutions are expected to participate in the study). 
 
7.0 
Methods 
7.1 Observation period 
From the start of treatment with Adcetris until the completion of 16 cycles [3 weeks per cycle] 
 
* Rationale for the selection of the observation period 
The assessment of the treatment cycle with the initial onset of adverse events in a clinical 
study [SGN35-006, the extended treatment group] evaluating the safety of Adcetris after Cycle 
17 showed a tendency that most adverse events occurred before Cycle 16. In addition, the 
types and severities did not differ between adverse events occurring after Cycle 17 and those 
occurring before Cycle 16. This suggested that the safety profile of Adcetris would be 
generally determined before Cycle 16. Therefore, the observation period was defined as the 
period from the start of treatment with Adcetris until the completion of 16 cycles. 
 
7.2 Request for participation in this study and contract with each study institution 
Paper-based case report forms will be used. To ask each study institution to participate in the 
study, the representative of Takeda Pharmaceutical Company Limited (representative of 
Takeda) will confirm before supply of Adcetris and the start of the study that each study 
institution meets all requirements for study institutions and investigators specified below, and 
have a written contract with the study institution after prior explanation of the study provided 
before supply of Adcetris. 
 
(1) Requirements for each study institution and investigator 
1) Requirements for each study institution 
[1] Is able to cooperate with this all-case surveillance and have a contract with the 
sponsor. 
[2] Is able to provide specialized treatment for hematopoietic tumors. 
[3] Is able to provide emergency treatment if required (including a case where such a 
treatment can be provided in conjunction with another institution 
). 

 
3 
* When emergency treatment is provided in conjunction with another institution, 
information on Adcetris safety measures and treatment of adverse drug reactions should 
be shared between the institution and the other institution to build a coalition. 
 
2) Requirements for each investigator 
[1] Has adequate knowledge and experience regarding the treatment of hematopoietic 
tumors, or is under the direction of a healthcare professional having such knowledge 
and experience. 
[2] Is able to cooperate with this all-case surveillance. 
 
 
(2) Prior explanation of the study to be provided before supply of Adcetris and the request for 
participation in this study 
Using “Request for Participation in the Special Drug Use Surveillance,” “Study Outline,” 
“Patient Enrollment Form (sample),” “Case Report Form Parts 1 and 2 (sample),” 
“Precautions for Use/Instruction Manual,” and “Proper Usage Guide,” the representative of 
Takeda will explain the purpose and methods (e.g., all-case surveillance) of this survey study 
and information regarding the proper use of Adcetris to the investigator and ask him/her to 
participate in the all-case surveillance. 
The representative of Takeda will also confirm with the investigator that the institution and 
the investigator meet all requirements. 
 
(3) Request for participation in this study and contract with each study institution 
The representative of Takeda will have a written contract with the study institution after 
obtaining their agreement to participate in this study Takeda Pharmaceutical Company 
Limited will inform the outsourced Adcetris supplier that the contract is concluded and 
Adcetris should be supplied to the study institution. The representative of Takeda will deliver 
patient enrollment forms to the investigator. 
 
7.3 Method of patient enrollment 
The central enrollment method via FAX will be used. For each patient scheduled to receive 
treatment with Adcetris after the date of the start of the term of the contract with the study 
institution, the investigator will complete patient enrollment by submitting the Patient 
Enrollment Form with information required for patient enrollment filled in (see Section 9.1) 
via FAX to the Central Enrollment Center (see Section 12.3) until noon of the day before the 
date of the expected initial dose of Adcetris. 
The Central Enrollment Center will review the Patient Enrollment Form and send the 
Enrollment Completion Notice to the investigator via FAX. After receiving the Enrollment 
Completion Notice, the investigator will initiate treatment with Adcetris. 
 

 
4 
The Case Report Form consists of Parts 1 and 2 per patient. 
The representative of Takeda will deliver Case Report Form Part 1, which is issued after 
enrollment confirmation by the Central Enrollment Center, to the investigator. Case Report 
Form Part 2 is issued after the completion of follow-up on Case Report Form Part 1. 
 
7.4 Completion and submission of the case report form 
For all patients requiring the completion of the case report form, the investigator will complete 
the case report form during the period from the start of treatment with Adcetris until the end of 
Cycle 4 and within 1 month after the end of Cycle 16, and submit it to the representative of 
Takeda. 
If treatment with Adcetris is discontinued for any reason before the end of the observation 
period, the investigator will complete the case report form within 1 month after the completion 
of required observation submit it to the representative of Takeda. If treatment with Adcetris is 
discontinued due to any adverse event, however, the investigator will continue to observe the 
patient after treatment discontinuation until the adverse event resolves or improves wherever 
possible, and then complete the case report form and submit it to the representative of Takeda. 
 
7.5 Confirmation of all-case surveillance 
After the completion of the study, the principal investigator will confirm that case report forms 
of all patients treated with Adcetris have been submitted, and sign or fill in his/her name with 
seal on All-Case Surveillance Confirmation Form and submit it to the representative of 
Takeda. 
 
8.0 
Estimated Study Period 
Study period: Starts on the day of the launch of Adcetris (April, 2014) and ends once the 
all-case surveillance is no longer a condition for approval of the product. 
Patient enrollment period: Starts on the day of the launch of Adcetris (April, 2014) and ends 
once the all-case surveillance is no longer a condition for approval of the 
product. 
 
The expected number of enrolled patients (140) was achieved. Therefore, the study will move 
to the period only requiring patient enrollment (not requiring the completion and submission 
of case report forms). 
After moving to the period only requiring patient enrollment, it may be required to complete 
and submit case report forms upon request by the regulatory authority. 
 
9.0 
Outcome Measures 
The investigator will record data listed below in both Patient Enrollment and Case Report 
Forms. Study schedule is provided in in Appendix 1. 

 
5 
9.1 Data to be recorded in Patient Enrollment Form 
1) Outcome measures 
Name of the institution, name of the investigator completing Patient Enrollment Form, 
expected date of the start of treatment with Adcetris, patient identification number, patient 
initial, sex, date of birth, diagnosis, performance status, CD30, past history of severe 
hypersensitivity to any ingredient of Adcetris, expected concomitant use of other 
antineoplastic drugs, and presence/absence of infections, peripheral nerve disorders, hepatic 
disorders, severe renal disorders, or pregnancy/breast-feeding 
2) When to collect outcome measure data 
At the time of patient enrollment 
 
9.2 Data to be recorded in Case Report Form 
 Cover sheet of Case Report Form 
9.2.1
Date of the finial completion of Case Report Form and name of the investigator completing 
Case Report Form 
 
 Patient demographics and baseline characteristics 
9.2.2
1) Outcome measures 
Date of diagnosis of Hodgkin's or anaplastic large cell lymphoma, site of involvement, 
ALK (in patients with anaplastic large cell lymphoma), clinical stage, presence/absence of 
B symptoms, ECOG Performance Status, therapeutic category, (presence/absence and 
detail of) hypersensitivity disposition, viral test results, past history of and concurrent 
pulmonary disorders, past history of and concurrent malignant tumours, (presence/absence 
and detail of) concurrent illnesses [other than pulmonary disorders and malignant tumours], 
(presence/absence and detail of) past history[other than pulmonary disorders and malignant 
tumours], height, weight, smoking history, and (presence/absence and detail of) prior 
treatment for Hodgkin's lymphoma or anaplastic large cell lymphoma (including drug 
therapy, radiotherapy, and hematopoietic stem cell transplantation) 
2) When to collect outcome measure data 
At the start of treatment with Adcetris 
 
 Treatment given 
9.2.3
1) Outcome measures 
Treatment with Adcetris and premedication to prevent infusion reaction (dose, date of 
premedication, and reasons for premedication to prevent infusion reaction and its 
discontinuation), (use or non-use, type, and date of) post-baseline hematopoietic stem cell 
transplantation, (presence/absence, name, and duration of) drugs other than Adcetris used 
for the treatment of the primary disease, and (presence/absence, name, and duration of) 
drugs used for the prevention of infection 
2) When to collect outcome measure data 

 
6 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Tests and assessments 
9.2.4
 Laboratory tests 
9.2.4.1
1) Outcome measures 
Red blood cell count, hemoglobin level, white blood cell count, neutrophil count, 
lymphocyte count, platelet count, total bilirubin, AST, ALT, LDH, BUN, and serum 
creatinine 
2) When to collect outcome measure data 
At each test time point during the period from the start of treatment with Adcetris until the 
completion of 16 cycles (or upon discontinuation of treatment with Adcetris) 
 
 Best response 
9.2.4.2
1) Outcome measures 
The best response (CR, CRu [for patients with no PET scan data], PR, SD, or PD) will be 
assessed based on CT and PET scans of the neck, chest, abdomen, and pelvis according to 
the best response assessment criteria (see Appendix). 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Date of the final observation 
9.2.4.3
1) Outcome measures 
Date of the final observation 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Other assessments 
9.2.4.4
1) Outcome measures 
Pregnancy during the observation period (for females only) 
If pregnancy is detected during the observation period, it should be reported to the 
representative of Takeda immediately. 
2) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Adverse events 
9.2.5
1) Outcome measures 

 
7 
Presence/absence of adverse events (see Table 1), adverse event terms, date of onset, 
CTCAE grade (the worst one), seriousness and its reason (see Table 2), (presence/absence 
and detail of) action taken to Adcetris, (presence/absence and detail of) intervention for 
adverse events, date of outcome, outcome, causal relationship with Adcetris* (see Table 3), 
and changes in laboratory test values associated with adverse events over time 
If the outcome is “not recovered/not resolved” or “unknown,” and the causal relationship 
with Adcetris is considered unevaluable, the event should be followed wherever possible. 
* If the event is considered not related to Adcetris, its rationale should be collected. If the causal 
relationship with Adcetris is considered unevaluable, its reason should be collected. 
Note) Points to consider regarding adverse events 
Worsening of the primary disease should not be regarded as an adverse event. However, abnormal 
worsening of the primary disease (e.g., worsening beyond the expected natural course of the 
disease) should be regarded as an adverse event. 
Disease progression should be regarded as worsening of the primary disease rather than an adverse 
event. However, clinical or laboratory progression of an existing cancer (including new metastasis) 
that meets any of the criteria for the seriousness of adverse events (see Table 2) should be 
considered a serious adverse event. 
2) Adverse events of particular interest 
The events listed below are events of particular interest; detailed information on these 
events should be collected wherever possible it they are observed:  
• Peripheral nerve disorders 
• Infections 
• Neutropenia 
• Infusion reactions 
• Pulmonary disorders 
 
* Rationale for the selection of adverse events of particular interest 
Of important identified risks listed in Risk Management Plan, those listed above were 
selected as adverse events of particular interest based on the following rationales: 
a) Peripheral nerve disorders 
Peripheral nerve disorders are frequently observed after treatment with Adcetris. If the 
event of peripheral nerve disorder becomes severe, it is difficult to continue treatment 
with Adcetris. It is important to control the onset of the event to allow for continuation of 
treatment (including dose reduction and restart of treatment after treatment interruption). 
Therefore, the profile of peripheral nerve disorders in Japanese patients as an adverse 
event of particular interest will be determined (i.e., information useful for continuation of 
treatment with Adcetris, including risk factors, commonly reported time to onset, 
outcomes, and the status of treatment with Adcetris, will be collected). 
b) Infections 

 
8 
It is expected that Adcetris is used in patients who are immunocompromised due to prior 
treatment or the prior disease or those who are complicated with infection, and the 
incidence of infections is likely to be high. Therefore, the profile of infections in Japanese 
patients as an adverse event of particular interest (i.e., the incidence and temporal 
relationship with the onset of neutropenia/lymphopenia) will be determined. 
c) Neutropenia 
It is expected that Adcetris is used in patients with decreased neutrophil count due to prior 
treatment, which may increase the risk of infection and result in a high incidence of 
infection/severe infection. It is important to control the neutrophil count to allow for 
continuation of treatment (including dose reduction and restart of treatment after 
treatment interruption) in terms of the prevention of infection. Therefore, the profile of 
neutropenia in Japanese patients as an adverse event of particular interest will be 
determined (i.e., the status of treatment with Adcetris and neutrophil count control will be 
assessed and information useful for continuation of treatment with Adcetris will be 
collected). 
d) Infusion reactions  
Infusion reactions are characteristic of monoclonal antibody preparations, the profile of 
infusion reactions in Japanese patients as an adverse event of particular interest (including 
the status of premedication and the percentage of patients using premedication to prevent 
infusion reactions [use/non-use of premedication to prevent infusion reactions]) will be 
determined. 
e) Pulmonary disorders 
The occurrence of pulmonary disorders in Japanese patients receiving monotherapy with 
Adcetris as an adverse event of particular interest will be determined. 
3) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 

 
9 
Table 1 Definition of an Adverse Event 
An adverse event (AE) is any untoward or undesirable medical occurrence in a patient linked in time 
with the use of a pharmaceutical/ medicinal product and which does not necessarily have to have a 
causal relationship with this treatment or may or may not be considered related to the product. 
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not related to the medicinal product. 
Adverse events also include: 
• Symptoms observed in an infant breast-fed by a mother receiving treatment with Adcetris. 
 
Table 2 Criteria for the Seriousness of Adverse Events 
An adverse event meeting any of the following criteria will be considered serious: 
1. Results in death. 
2. Is life-threatening. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization. 
4. Results in persistent or significant disability/incapacity. 
5. Is a congenital anomaly/birth defect. 
6. Is a medically important condition due to any of the above 1 to 5, including those listed in “Takeda 
Medically Significant AE List.” 
 
Takeda Medically Significant AE List 
• Acute respiratory failure/acute respiratory distress 
syndrome (ARDS) 
• Anaphylactic shock 
• Torsade de pointes/ventricular fibrillation/ventricular 
tachycardia 
• Acute kidney failure 
• Malignant hypertension                 
• Pulmonary hypertension 
• Convulsive seizure (including convulsion and epilepsy) 
• Pulmonary fibrosis (including interstitial 
pneumonia) 
• Agranulocytosis 
• Neuroleptic malignant 
syndrome/malignant hyperthermia 
• Aplastic anemia 
• Spontaneous abortion/stillbirth and fetal 
death 
• Toxic epidermal necrolysis/oculomucocutaneous 
syndrome (Stevens-Johnson syndrome) 
• (Suspected) transmission of infection via a 
drug 
• Hepatic necrosis 
• (Suspected) endotoxic shock 
• Acute hepatic failure                    
 
 

 
10 
Table 3 Criteria for the Assessment of Causal Relationship between Adverse Events and 
Adcetris 
Causality 
Assessment criterion 
Related 
There is a temporal relationship between the event and Adcetris (and 
the clinical course after treatment discontinuation). Or, there are other 
contributing factors, such as the primary disease, concurrent illnesses, 
and concomitant medications/therapies, but it is also likely that the 
event is attributable to Adcetris. 
Not related 
There is no temporal relationship between the event and Adcetris. Or, 
it is very likely that the event is attributable to other factors, such as 
the primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
Indeterminate 
There is limited information required for the assessment of causal 
relationship, such as temporal relationship between the event and 
Adcetris (and the clinical course after treatment discontinuation), the 
primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
 
10.0 
Data to Be Analyzed and Methods of Analysis 
10.1 Patient disposition 
Data to be analyzed includes the number of enrolled patients, the number of patients whose 
case report forms are available, and the number of patients included in and excluded from the 
safety/efficacy analysis set and reasons for inclusion/exclusion. 
 
10.2 Patient demographics and baseline characteristics 
Data to be analyzed includes sex, age, disease duration, site of involvement, and clinical stage. 
 
10.3 Treatment given 
Data to be analyzed includes the status of treatment with Adcetris and concomitant 
medications. 
 
10.4 Safety 
The measures specified below will be analyzed using the safety analysis set. Adverse events 
will be coded using MedDRA/J and summarized using (Preferred Terms [PTs]) and System 
Organ Classes [SOCs]). 
 Occurrence of adverse events 
10.4.1
The frequency of adverse events observed during the observation period will be analyzed 
by type, time of onset, seriousness, and Adcetris. 
 

 
11 
 Factors that may affect the safety of Adcetris 
10.4.2
The frequency of adverse events observed during the observation period will be analyzed 
by patient background factors (sex, age, presence/absence of concurrent renal disorders, 
and presence/absence of concurrent hepatic disorders) and treatment given (the status of 
treatment with Adcetris and concomitant medications). 
 
 Changes in laboratory test data over time 
10.4.3
Summary statistics of laboratory test values at baseline and post-baseline will be calculated. 
 
10.5 Efficacy 
The measures specified below will be analyzed using the efficacy analysis set. 
 Best response 
10.5.1
The best response after 16 cycles of treatment with Adcetris (or upon discontinuation of 
treatment with Adcetris) will be analyzed. 
 
 Overall survival 
10.5.2
The time to death (regardless of the cause of death) will be analyzed using the “final 
observation date” in specified in Section 9.2.4.3 as the date of survival confirmation and the 
date of outcome of an adverse event with “Died/fetal” recorded in the Outcome field 
specified in Section 9.2.5 as the date of death 
 
10.6 Interim analyses 
For patients whose case report forms are collected through November 30, 2014 with evaluable 
safety evaluation, analyses similar to the ones described in Sections 10.1 to 10.4 will be 
performed to evaluate and analyze safety information obtained in this study at an early stage 
and publish them as appropriate. 
 
11.0 
Posting of Information Regarding This Study 
Prior to the start of the study, Takeda Pharmaceutical Company Limited will register 
information regarding this study to the public website specified below. 
 
Japan Pharmaceutical Information Center-Clinical Trials Information 
 
ClinicalTrials.gov (a clinical trial registration system provided by the National Institutes of Health) 
 
12.0 
Organizational Structure 
12.1 Person responsible for administration 
, Takeda Pharmaceutical Company Limited 
 
12.2 Proper Use Committee 
The committee will provide advice on the protocol, data analysis, publication of study results, 
promotion of the proper use of Adcetris, and safety measures. 
PPD

 
12 
(Listed in the order of the Japanese syllabary) 
 
12.3 Central Enrollment Center 
 
 
13.0 
Contract Research Organization 
 
14.0 
Other Important Information 
14.1 Protocol amendment 
During the study, the sponsor will monitor the occurrence of adverse drug reactions and 
serious adverse drug reactions that cannot be predicted by the progress of the study and 
precautions for use, the presence/absence of an increase in the frequency of specific adverse 
drug reactions, and the appropriateness of outcome measures, and review and amend this 
protocol as appropriate. If the approval of partial changes to “Dosage and Administration” or 
“Indication” is obtained during the study, the sponsor will consider the necessity of 
amendment of this protocol as appropriate, and amend the protocol as appropriate. 
 
14.2 Measures to be taken in response to issues/questions 
If any safety and/or efficacy issue is detected, the sponsor will examine data closely and 
consider what measures should be taken. 
 
 
 
PPD
PPD
PPD

 
13 
         Time point 
 
 
   Procedure 
Observation period 
At the time 
of patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Patient enrollment 
Date of the expected initial dose of Adcetris 
○ 
 
 
 
 
Patient identification number 
○ 
Patient initial 
○ 
 
Sex 
○ 
Date of birth 
○ 
Diagnosis 
○ 
Performance status 
○ 
 
 
 
CD30 
○ 
 
 
 
Past history of severe hypersensitivity to any 
ingredient of Adcetris 
○ 
 
 
 
Expected concomitant use of other 
antineoplastic drugs 
○ 
 
 
 
Presence/absence of infections 
○ 
 
 
 
 
Presence/absence of peripheral nerve 
disorders 
○ 
 
 
 
Presence/absence of hepatic disorders 
○ 
 
 
 
Presence/absence of severe renal disorders 
○ 
 
 
 
Presence/absence of pregnancy/breast-feeding 
○ 
 
 
 
Patient demographics and baseline characteristics 
Date of diagnosis of Hodgkin or anaplastic 
large-cell lymphoma 
○ 
 
 
Site of involvement 
○ 
 
 
ALK (in patients with anaplastic large cell 
lymphoma) 
○ 
 
 
Clinical stage 
○ 
 
 
Presence/absence of B symptoms 
○ 
 
 
ECOG Performance Status 
 
○ 
 
 
 
Therapeutic category 
 
○ 
 
 
Hypersensitivity disposition 
 
○ 
 
 
Viral test results 
 
○ 
 
 
Past history of and concurrent pulmonary 
disorders 
 
○ 
 
 
Past history of and concurrent malignant 
tumours 
 
○ 
 
 
Concurrent illness (other than pulmonary 
disorders and malignant tumours) 
 
○ 
 
 
Past history (other than pulmonary disorders 
and malignant tumours) 
 
○ 
 
 
 
Height and weight 
 
○ 
 
 
Smoking history 
 
○ 
 
 
Prior treatment for Hodgkin's or anaplastic 
large cell lymphoma 
 
○ 
 
 
 
Appendix 1 Study Schedule 

 
14 
 
 
         Time point 
 
 
   Procedure 
Observation period 
At the time 
of patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Treatment given 
Treatment with Adcetris 
 
○ 
○ 
 
 
Post-baseline hematopoietic stem cell 
transplantation 
 
○ 
○ 
Drug(s) other than Adcetris used for the 
treatment of the primary disease 
 
○ 
○ 
Drug(s) used for the prevention of infection 
 
○ 
○ 
Tests and assessments 
Laboratory tests (red blood cell count, 
hemoglobin level, white blood cell count, 
neutrophil count, lymphocyte count, platelet 
count, and liver and kidney function tests) 
 
 
○ 
○ 
Best response 
 
 
○ 
○ 
Date of the final observation 
 
 
 
○ 
○ 
Presence/absence of pregnancy (for females 
only) 
 
○ 
○ 
Adverse events 
 
○ 
○ 
   ○   : Data collected 
   ○   : Data collected throughout the period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
15 
Appendix 2 Best Response Assessment Criteria (Revised Response Criteria for Malignant Lymphoma*)  
* Extracted from “General Rules for the Clinical and Pathological Studies on Tumors of Hematopoietic and 
Lymphoid Tissues, March 2000 [First Edition]) 
For patients with PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
 The patient is PET negative. If the patient is PET negative, any residual tumor on CT does not matter. 
1)-2Variably FDG-avid lymphoma 
 The patient did not undergo PET before treatment. If the patient was negative before treatment, the patient 
must meet all the following criteria: 
 [1] All nodal target lesions are normal. 
 [2] All extranodal target lesions have resolved. 
 [3] All nodal non-target lesions are normal. 
 [4] The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
 [5] All extranodal non-target lesions have resolved. 
2) A patient with bone marrow infiltration at baseline must be negative for bone marrow infiltration. A patient 
with no bone marrow infiltration at baseline should be regarded as “negative” because bone marrow test is 
not required. 
3) The patient has no new lesion. 
PR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
If the patient had one or more PET positive lesions, or was PET negative AND had bone marrow infiltration 
at baseline, the patient must be positive for bone marrow infiltration at the time of restaging (or have not 
undergone testing). 
1)-2Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
3) All nodal non-target lesions are normal or free from enlargement. 
4) All extranodal non-target lesions have resolved or free from enlargement. 
5) Bone marrow infiltration does not matter. Testing is not required. 
6) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR but meets any of the criteria 1 and 2 to 6 and 7 listed below, the 
patient will be assessed as having progressive disease (PD). If the patient meets any of the criteria listed below 
after being assessed as achieving CR, the patient will be assessed as having a relapsed disease (RD): 
1)-1 Routinely FDG-avid lymphoma 
 The patient has one or more PET positive lesions. 
1)-2 Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
3) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 

 
16 
diameter) or re-enlargement. 
4) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
5) The long diameter of the nodal target lesion which was once normalized and assessed as CR exceeded 1.5 
cm. The extranodal target lesion which once resolved reappeared. 
6) The patient has a new lesion. 
7) The patient became positive after being once negative for bone marrow infiltration. 
 
 
For patients with no PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
5) All extranodal non-target lesions have resolved. 
6) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
7) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
8) A patient with bone marrow infiltration or indeterminate at baseline must be negative for bone marrow 
infiltration. 
 A patient with no bone marrow infiltration at baseline should be regarded as “negative” because bone 
marrow test is not required. 
9) The patient has no new lesion. 
CRu   
The patient had bone marrow infiltration or was indeterminate at baseline AND meets all the following 
criteria: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) All extranodal non-target lesions have resolved. 
5) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
6) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
7) The patient is indeterminate for bone marrow infiltration. 
8) The patient has no new lesion. 
 
OR 
1) The patient has a 75% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal. 
3) All extranodal non-target lesions have resolved. 
4) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
5) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
6) The patient has no bone marrow infiltration or indeterminate. 

 
17 
7) The patient has no new lesion. 
PR 
The patient meets all the above criteria for CRu except for criterion 6. A patient with bone marrow infiltration 
or indeterminate at baseline must be positive for bone marrow infiltration at the time of restaging. 
Or, the patient meets all the following criteria: 
1) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal or free from enlargement. 
3) All extranodal non-target lesions have resolved or free from enlargement. 
4) Enlarged liver, spleen, and kidneys have resolved or are free from progression. 
5) All tumor-related symptom (fever and night sweat) have resolved. AND abnormal tumor-related laboratory 
test results (tumor-related increase in LDH) became normal. 
6) Bone marrow infiltration does not matter. Testing is not required. 
7) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR or CRu but meets any of the criteria below, the patient will be 
assessed as having progressive disease (PD). If the patient meets any of the criteria listed below after being 
assessed as achieving CR or CRu, the patient will be assessed as having a relapsed disease (RD): 
1) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
2) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 
diameter) or re-enlargement. 
3) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
4) The extranodal target lesion which once resolved and was assesses as CR or CRu reappeared. 
5) Obvious progression or recurrence of enlarged liver, spleen, or kidney. 
6) Obvious progression or recurrence of tumor-related subjective and objective symptoms (fever and night 
sweat) or abnormal tumor-related laboratory test results (tumor-related increase in LDH). 
7) The patient became positive after being once negative for bone marrow infiltration. 
8) The patient has a new lesion. 
 

 
 
 
 
 
Special Drug Use Surveillance Protocol 
Special Drug Use Surveillance of Adcetris IV Infusion 
(All-Case Surveillance) 
“Relapsed or Refractory CD30+ Hodgkin's Lymphoma 
or Anaplastic Large Cell Lymphoma” 
 
 
 
 
 
 
 
 
Version number 
2 
Date of creation 
August 25, 2014 
Sponsor 
Takeda Pharmaceutical Company Limited 
 

 
Table of Contents 
1.0 
Background ..................................................................................................................................... 1 
2.0 
Purpose ............................................................................................................................................ 1 
3.0 
Estimated Enrollment and Its Rationale ...................................................................................... 1 
3.1 
Estimated enrollment ................................................................................................................. 1 
3.2 
Rationale ...................................................................................................................................... 1 
4.0 
Eligible Patients ............................................................................................................................. 1 
5.0 
Dosage Regimen .............................................................................................................................. 2 
6.0 
Expected Study Institutions by Department ................................................................................ 2 
7.0 
Methods ........................................................................................................................................... 2 
7.1 
Observation period ...................................................................................................................... 2 
7.2 
Request for participation in this study and contract with each study institution ................. 2 
7.3 
Method of patient enrollment..................................................................................................... 3 
7.4 
Completion and submission of the case report form ................................................................ 4 
7.5 
Confirmation of all-case surveillance ........................................................................................ 4 
8.0 
Estimated Study Period ................................................................................................................. 4 
9.0 
Outcome Measures ......................................................................................................................... 4 
9.1 
Data to be recorded in Patient Enrollment Form ..................................................................... 4 
9.2 
Data to be recorded in Case Report Form ................................................................................. 5 
 
Cover sheet of Case Report Form ....................................................................................... 5 
9.2.1
 
Patient demographics and baseline characteristics .......................................................... 5 
9.2.2
 
Treatment given ................................................................................................................... 5 
9.2.3
 
Tests and assessments ......................................................................................................... 6 
9.2.4
 
Laboratory tests ............................................................................................................... 6 
9.2.4.1
 
Best response .................................................................................................................... 6 
9.2.4.2
 
Date of the final observation ........................................................................................... 6 
9.2.4.3
 
Other assessments ........................................................................................................... 6 
9.2.4.4
 
Adverse events ..................................................................................................................... 6 
9.2.5
10.0 Data to Be Analyzed and Methods of Analysis ........................................................................... 10 
10.1 Patient disposition .................................................................................................................... 10 
10.2 Patient demographics and baseline characteristics ............................................................... 10 
10.3 Treatment given ........................................................................................................................ 10 
10.4 Safety ......................................................................................................................................... 10 
 
Occurrence of adverse events ............................................................................................ 10 
10.4.1
 
Factors that may affect the safety of Adcetris ................................................................. 11 
10.4.2
 
Changes in laboratory test data over time ...................................................................... 11 
10.4.3
10.5 Efficacy ....................................................................................................................................... 11 
 
Best response ..................................................................................................................... 11 
10.5.1
 
Overall survival ................................................................................................................. 11 
10.5.2
10.6 Interim analyses ....................................................................................................................... 11 

 
11.0 
Posting of Information Regarding This Study ............................................................................ 11 
12.0 Organizational Structure ............................................................................................................. 11 
12.1 Person responsible for administration .................................................................................... 11 
12.2 Proper Use Committee .............................................................................................................. 12 
12.3 Central Enrollment Center ...................................................................................................... 12 
13.0 Contract Research Organization ................................................................................................. 12 
14.0 Other Important Information ...................................................................................................... 12 
14.1 Protocol amendment ................................................................................................................. 12 
14.2 Measures to be taken in response to issues/questions ........................................................... 12 
 
Appendices  
   Appendix 1 Study Schedule................................................................................................................................ 13 
   Appendix 2 Best Response Assessment Criteria................................................................................................. 15 
 

 
1 
1.0 
Background 
There is limited safety information on Adcetris IV Infusion 50 mg (hereinafter referred to as 
Adcetris) collected from Japanese patients in Japanese phase 1/2 studies. It is important to 
promptly collect post-marketing safety information and provide it to healthcare providers. It 
was also deemed that additional surveillance was required to determine the occurrence of 
peripheral nerve disorders, infections, neutropenia, infusion reactions, and pulmonary 
disorders in patients using Adcetris in Japan as post-marketing safety specifications. 
Thus, an all-case surveillance in all patients receiving treatment with Adcetris will be initiated 
as an additional pharmacovigilance activity for Adcetris when the drug is launched. 
This surveillance study will be conducted in compliance with the GPSP Ordinance and other 
related regulatory requirements. 
 
2.0 
Purpose 
The purpose of this study is to evaluate the safety of Adcetris in patients with 
relapsed/refractoryCD30+ Hodgkin's lymphoma or anaplastic large cell lymphoma in the 
routine clinical setting, as well as to collect efficacy information for reference. 
 
3.0 
Estimated Enrollment and Its Rationale 
3.1 Estimated enrollment  
140 patients (with relapsed/refractory CD30+ Hodgkin's lymphoma or anaplastic large cell 
lymphoma) 
 
3.2 Rationale 
It is expected that the detailed evaluation of peripheral nerve disorders, infections, neutropenia, 
infusion reactions, and pulmonary disorders will help better understand the safety profile of 
Adcetris in the routine clinical setting, which will lead to the assessment of the risk-benefit 
balance of the drug. 
The frequencies of peripheral nerve disorders, infections, neutropenia (≥Grade 3), infusion 
reaction, and pulmonary disorder in non-Japanese phase 2 studies (pooled study data from a 
study in patients with Hodgkin's lymphoma [SG035-0003, 102 patients] and a study in 
patients with systemic anaplastic large cell lymphoma [SG035-0004, 58 patients]) were 56%, 
61%, 20%, 11%, and 6%, respectively. 
Observation of infusion reactions with the lowest frequency of ≥10 patients, aside from 
pulmonary disorders, with a probability of 95% would require 140 patients, which was 
therefore determined to be the estimated enrollment. It is estimated that when the number of 
patients enrolled reaches 140 patients, ≥4 patients have adverse events of pulmonary disorder 
with a probability of 95%. 
 
4.0 
Eligible Patients 
All patients receiving treatment with Adcetris 

 
2 
 
5.0 
Dosage Regimen 
The usual adult dosage is 1.8 mg/kg (body weight) of brentuximab vedotin (recombinant) 
infused intravenously once every three weeks. The dose should be adjusted depending on the 
patient's condition. 
See the "PRECAUTIONS" section of the package insert. 
 
6.0 
Expected Study Institutions by Department 
The study will be conducted at all institutions using Adcetris (e.g., department of hematology) 
(approximately 100 study institutions are expected to participate in the study). 
 
7.0 
Methods 
7.1 Observation period 
From the start of treatment with Adcetris until the completion of 16 cycles [3 weeks per cycle] 
 
* Rationale for the selection of the observation period 
The assessment of the treatment cycle with the initial onset of adverse events in a clinical 
study [SGN35-006, the extended treatment group] evaluating the safety of Adcetris after Cycle 
17 showed a tendency that most adverse events occurred before Cycle 16. In addition, the 
types and severities did not differ between adverse events occurring after Cycle 17 and those 
occurring before Cycle 16. This suggested that the safety profile of Adcetris would be 
generally determined before Cycle 16. Therefore, the observation period was defined as the 
period from the start of treatment with Adcetris until the completion of 16 cycles. 
 
7.2 Request for participation in this study and contract with each study institution 
Paper-based case report forms will be used. To ask each study institution to participate in the 
study, the medical representative of Takeda Pharmaceutical Company Limited (Takeda MR) 
will confirm before supply of Adcetris and the start of the study that each study institution 
meets all requirements for study institutions and investigators specified below, and have a 
written contract with the study institution after prior explanation of the study provided before 
supply of Adcetris. 
 
(1) Requirements for each study institution and investigator 
1) Requirements for each study institution 
[1] Is able to cooperate with this all-case surveillance and have a contract with the 
sponsor. 
[2] Is able to provide specialized treatment for hematopoietic tumors. 
[3] Is able to provide emergency treatment if required (including a case where such a 
treatment can be provided in conjunction with another institution 
). 

 
3 
* When emergency treatment is provided in conjunction with another institution, 
information on Adcetris safety measures and treatment of adverse drug reactions should 
be shared between the institution and the other institution to build a coalition. 
 
2) Requirements for each investigator 
[1] Has adequate knowledge and experience regarding the treatment of hematopoietic 
tumors, or is under the direction of a healthcare professional having such knowledge 
and experience. 
[2] Is able to cooperate with this all-case surveillance. 
 
 
(2) Prior explanation of the study to be provided before supply of Adcetris and the request for 
participation in this study 
Using “Request for Participation in the Special Drug Use Surveillance,” “Study Outline,” 
“Patient Enrollment Form (sample),” “Case Report Form Parts 1 and 2 (sample),” 
“Precautions for Use/Instruction Manual,” and “Proper Usage Guide,” the Takeda MR will 
explain the purpose and methods (e.g., all-case surveillance) of this survey study and 
information regarding the proper use of Adcetris to the investigator and ask him/her to 
participate in the all-case surveillance. 
The Takeda MR will also confirm with the investigator that the institution and the 
investigator meet all requirements. 
 
(3) Request for participation in this study and contract with each study institution 
The Takeda MR will have a written contract with the study institution after obtaining their 
agreement to participate in this study Takeda Pharmaceutical Company Limited will inform 
the outsourced Adcetris supplier that the contract is concluded and Adcetris should be 
supplied to the study institution. The Takeda MR will deliver patient enrollment forms to the 
investigator. 
 
7.3 Method of patient enrollment 
The central enrollment method via FAX will be used. For each patient scheduled to receive 
treatment with Adcetris after the date of the start of the term of the contract with the study 
institution, the investigator will complete patient enrollment by submitting the Patient 
Enrollment Form with information required for patient enrollment filled in (see Section 9.1) 
via FAX to the Central Enrollment Center (see Section 12.3) until noon of the day before the 
date of the expected initial dose of Adcetris. 
The Central Enrollment Center will review the Patient Enrollment Form and send the 
Enrollment Completion Notice to the investigator via FAX. After receiving the Enrollment 
Completion Notice, the investigator will initiate treatment with Adcetris. 
 

 
4 
The Case Report Form consists of Parts 1 and 2 per patient. 
The Takeda MR will deliver Case Report Form Part 1, which is issued after enrollment 
confirmation by the Central Enrollment Center, to the investigator. Case Report Form Part 2 is 
issued after the completion of follow-up on Case Report Form Part 1. 
 
7.4 Completion and submission of the case report form 
For all patients requiring the completion of the case report form, the investigator will complete 
the case report form during the period from the start of treatment with Adcetris until the end of 
Cycle 4 and within 1 month after the end of Cycle 16, and submit it to the Takeda MR. 
If treatment with Adcetris is discontinued for any reason before the end of the observation 
period, the investigator will complete the case report form within 1 month after the completion 
of required observation submit it to the Takeda MR. If treatment with Adcetris is discontinued 
due to any adverse event, however, the investigator will continue to observe the patient after 
treatment discontinuation until the adverse event resolves or improves wherever possible, and 
then complete the case report form and submit it to the Takeda MR. 
 
7.5 Confirmation of all-case surveillance 
After the completion of the study, the principal investigator will confirm that case report forms 
of all patients treated with Adcetris have been submitted, and sign or fill in his/her name with 
seal on All-Case Surveillance Confirmation Form and submit it to the Takeda MR. 
 
8.0 
Estimated Study Period 
Study period: Starts on the day of the launch of Adcetris (April, 2014) and ends once the 
all-case surveillance is no longer a condition for approval of the product. 
Patient enrollment period: Starts on the day of the launch of Adcetris (April, 2014) and ends 
once the all-case surveillance is no longer a condition for approval of the 
product. 
 
The expected number of enrolled patients (140) was achieved. Therefore, the study will move 
to the period only requiring patient enrollment (not requiring the completion and submission 
of case report forms). 
After moving to the period only requiring patient enrollment, it may be required to complete 
and submit case report forms upon request by the regulatory authority. 
 
9.0 
Outcome Measures 
The investigator will record data listed below in both Patient Enrollment and Case Report 
Forms. Study schedule is provided in in Appendix 1. 
9.1 Data to be recorded in Patient Enrollment Form 
1) Outcome measures 
Name of the institution, name of the investigator completing Patient Enrollment Form, 

 
5 
expected date of the start of treatment with Adcetris, patient identification number, patient 
initial, sex, date of birth, diagnosis, performance status, CD30, past history of severe 
hypersensitivity to any ingredient of Adcetris, expected concomitant use of other 
antineoplastic drugs, and presence/absence of infections, peripheral nerve disorders, hepatic 
disorders, severe renal disorders, or pregnancy/breast-feeding 
2) When to collect outcome measure data 
At the time of patient enrollment 
 
9.2 Data to be recorded in Case Report Form 
 Cover sheet of Case Report Form 
9.2.1
Date of the finial completion of Case Report Form and name of the investigator completing 
Case Report Form 
 
 Patient demographics and baseline characteristics 
9.2.2
1) Outcome measures 
Date of diagnosis of Hodgkin's or anaplastic large cell lymphoma, site of involvement, 
ALK (in patients with anaplastic large cell lymphoma), clinical stage, presence/absence of 
B symptoms, ECOG Performance Status, therapeutic category, (presence/absence and 
detail of) hypersensitivity disposition, viral test results, past history of and concurrent 
pulmonary disorders, past history of and concurrent malignant tumours, (presence/absence 
and detail of) concurrent illnesses [other than pulmonary disorders and malignant tumours], 
(presence/absence and detail of) past history[other than pulmonary disorders and malignant 
tumours], height, weight, smoking history, and (presence/absence and detail of) prior 
treatment for Hodgkin's lymphoma or anaplastic large cell lymphoma (including drug 
therapy, radiotherapy, and hematopoietic stem cell transplantation) 
2) When to collect outcome measure data 
At the start of treatment with Adcetris 
 
 Treatment given 
9.2.3
1) Outcome measures 
Treatment with Adcetris and premedication to prevent infusion reaction (dose, date of 
premedication, and reasons for premedication to prevent infusion reaction and its 
discontinuation), (use or non-use, type, and date of) post-baseline hematopoietic stem cell 
transplantation, (presence/absence, name, and duration of) drugs other than Adcetris used 
for the treatment of the primary disease, and (presence/absence, name, and duration of) 
drugs used for the prevention of infection 
2) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 

 
6 
 Tests and assessments 
9.2.4
 Laboratory tests 
9.2.4.1
1) Outcome measures 
Red blood cell count, hemoglobin level, white blood cell count, neutrophil count, 
lymphocyte count, platelet count, total bilirubin, AST, ALT, LDH, BUN, and serum 
creatinine 
2) When to collect outcome measure data 
At each test time point during the period from the start of treatment with Adcetris until the 
completion of 16 cycles (or upon discontinuation of treatment with Adcetris) 
 
 Best response 
9.2.4.2
1) Outcome measures 
The best response (CR, CRu [for patients with no PET scan data], PR, SD, or PD) will be 
assessed based on CT and PET scans of the neck, chest, abdomen, and pelvis according to 
the best response assessment criteria (see Appendix). 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Date of the final observation 
9.2.4.3
1) Outcome measures 
Date of the final observation 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Other assessments 
9.2.4.4
1) Outcome measures 
Pregnancy during the observation period (for females only) 
If pregnancy is detected during the observation period, it should be reported to the Takeda 
MR immediately. 
2) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Adverse events 
9.2.5
1) Outcome measures 
Presence/absence of adverse events (see Table 1), adverse event terms, date of onset, 
CTCAE grade (the worst one), seriousness and its reason (see Table 2), (presence/absence 
and detail of) action taken to Adcetris, (presence/absence and detail of) intervention for 

 
7 
adverse events, date of outcome, outcome, causal relationship with Adcetris* (see Table 3), 
and changes in laboratory test values associated with adverse events over time 
If the outcome is “not recovered/not resolved” or “unknown,” and the causal relationship 
with Adcetris is considered unevaluable, the event should be followed wherever possible. 
* If the event is considered not related to Adcetris, its rationale should be collected. If the causal 
relationship with Adcetris is considered unevaluable, its reason should be collected. 
Note) Points to consider regarding adverse events 
Worsening of the primary disease should not be regarded as an adverse event. However, abnormal 
worsening of the primary disease (e.g., worsening beyond the expected natural course of the 
disease) should be regarded as an adverse event. 
Disease progression should be regarded as worsening of the primary disease rather than an adverse 
event. However, clinical or laboratory progression of an existing cancer (including new metastasis) 
that meets any of the criteria for the seriousness of adverse events (see Table 2) should be 
considered a serious adverse event. 
2) Adverse events of particular interest 
The events listed below are events of particular interest; detailed information on these 
events should be collected wherever possible it they are observed:  
• Peripheral nerve disorders 
• Infections 
• Neutropenia 
• Infusion reactions 
• Pulmonary disorders 
 
* Rationale for the selection of adverse events of particular interest 
Of important identified risks listed in Risk Management Plan, those listed above were 
selected as adverse events of particular interest based on the following rationales: 
a) Peripheral nerve disorders 
Peripheral nerve disorders are frequently observed after treatment with Adcetris. If the 
event of peripheral nerve disorder becomes severe, it is difficult to continue treatment 
with Adcetris. It is important to control the onset of the event to allow for continuation of 
treatment (including dose reduction and restart of treatment after treatment interruption). 
Therefore, the profile of peripheral nerve disorders in Japanese patients as an adverse 
event of particular interest will be determined (i.e., information useful for continuation of 
treatment with Adcetris, including risk factors, commonly reported time to onset, 
outcomes, and the status of treatment with Adcetris, will be collected). 
b) Infections 
It is expected that Adcetris is used in patients who are immunocompromised due to prior 
treatment or the prior disease or those who are complicated with infection, and the 
incidence of infections is likely to be high. Therefore, the profile of infections in Japanese 

 
8 
patients as an adverse event of particular interest (i.e., the incidence and temporal 
relationship with the onset of neutropenia/lymphopenia) will be determined. 
c) Neutropenia 
It is expected that Adcetris is used in patients with decreased neutrophil count due to prior 
treatment, which may increase the risk of infection and result in a high incidence of 
infection/severe infection. It is important to control the neutrophil count to allow for 
continuation of treatment (including dose reduction and restart of treatment after 
treatment interruption) in terms of the prevention of infection. Therefore, the profile of 
neutropenia in Japanese patients as an adverse event of particular interest will be 
determined (i.e., the status of treatment with Adcetris and neutrophil count control will be 
assessed and information useful for continuation of treatment with Adcetris will be 
collected). 
d) Infusion reactions  
Infusion reactions are characteristic of monoclonal antibody preparations, the profile of 
infusion reactions in Japanese patients as an adverse event of particular interest (including 
the status of premedication and the percentage of patients using premedication to prevent 
infusion reactions [use/non-use of premedication to prevent infusion reactions]) will be 
determined. 
e) Pulmonary disorders 
The occurrence of pulmonary disorders in Japanese patients receiving monotherapy with 
Adcetris as an adverse event of particular interest will be determined. 
3) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 

 
9 
Table 1 Definition of an Adverse Event 
An adverse event (AE) is any untoward or undesirable medical occurrence in a patient linked in time 
with the use of a pharmaceutical/ medicinal product and which does not necessarily have to have a 
causal relationship with this treatment or may or may not be considered related to the product. 
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not related to the medicinal product. 
Adverse events also include: 
・Symptoms observed in an infant breast-fed by a mother receiving treatment with Adcetris. 
 
Table 2 Criteria for the Seriousness of Adverse Events 
An adverse event meeting any of the following criteria will be considered serious: 
1. Results in death. 
2. Is life-threatening. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization. 
4. Results in persistent or significant disability/incapacity. 
5. Is a congenital anomaly/birth defect. 
6. Is a medically important condition due to any of the above 1 to 5, including those listed in “Takeda 
Medically Significant AE List.” 
 
Takeda Medically Significant AE List 
•Acute respiratory failure/acute respiratory distress 
syndrome (ARDS) 
•Anaphylactic shock 
•Torsade de pointes/ventricular fibrillation/ventricular 
tachycardia 
•Acute kidney failure 
•Malignant hypertension 
•Pulmonary hypertension 
•Convulsive seizure (including convulsion and 
epilepsy) 
•Pulmonary fibrosis (including interstitial 
pneumonia) 
•Agranulocytosis 
•Neuroleptic malignant syndrome/malignant 
hyperthermia 
•Aplastic anemia 
•Spontaneous abortion/stillbirth and fetal 
death 
•Toxic epidermal necrolysis/oculomucocutaneous 
syndrome (Stevens-Johnson syndrome) 
•(Suspected) transmission of infection via a 
drug  
•Hepatic necrosis 
•(Suspected) endotoxic shock or  
•Acute hepatic failure 
 
 

 
10 
Table 3 Criteria for the Assessment of Causal Relationship between Adverse Events and 
Adcetris 
Causality 
Assessment criterion 
Related 
There is a temporal relationship between the event and Adcetris (and 
the clinical course after treatment discontinuation). Or, there are other 
contributing factors, such as the primary disease, concurrent illnesses, 
and concomitant medications/therapies, but it is also likely that the 
event is attributable to Adcetris. 
Not related 
There is no temporal relationship between the event and Adcetris. Or, 
it is very likely that the event is attributable to other factors, such as 
the primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
Indeterminate 
There is limited information required for the assessment of causal 
relationship, such as temporal relationship between the event and 
Adcetris (and the clinical course after treatment discontinuation), the 
primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
 
10.0 
Data to Be Analyzed and Methods of Analysis 
10.1 Patient disposition 
Data to be analyzed includes the number of enrolled patients, the number of patients whose 
case report forms are available, and the number of patients included in and excluded from the 
safety/efficacy analysis set and reasons for inclusion/exclusion. 
 
10.2 Patient demographics and baseline characteristics 
Data to be analyzed includes sex, age, disease duration, site of involvement, and clinical stage. 
 
10.3 Treatment given 
Data to be analyzed includes the status of treatment with Adcetris and concomitant 
medications. 
 
10.4 Safety 
The measures specified below will be analyzed using the safety analysis set. Adverse events 
will be coded using MedDRA/J and summarized using (Preferred Terms [PTs]) and System 
Organ Classes [SOCs]). 
 Occurrence of adverse events 
10.4.1
The frequency of adverse events observed during the observation period will be analyzed 
by type, time of onset, seriousness, and Adcetris. 
 

 
11 
 Factors that may affect the safety of Adcetris 
10.4.2
The frequency of adverse events observed during the observation period will be analyzed 
by patient background factors (sex, age, presence/absence of concurrent renal disorders, 
and presence/absence of concurrent hepatic disorders) and treatment given (the status of 
treatment with Adcetris and concomitant medications). 
 
 Changes in laboratory test data over time 
10.4.3
Summary statistics of laboratory test values at baseline and post-baseline will be calculated. 
 
10.5 Efficacy 
The measures specified below will be analyzed using the efficacy analysis set. 
 Best response 
10.5.1
The best response after 16 cycles of treatment with Adcetris (or upon discontinuation of 
treatment with Adcetris) will be analyzed. 
 
 Overall survival 
10.5.2
The time to death (regardless of the cause of death) will be analyzed using the “final 
observation date” in specified in Section 9.2.4.3 as the date of survival confirmation and the 
date of outcome of an adverse event with “Died/fetal” recorded in the Outcome field 
specified in Section 9.2.5 as the date of death 
 
10.6 Interim analyses 
For patients whose case report forms are collected through November 30, 2014 with evaluable 
safety evaluation, analyses similar to the ones described in Sections 10.1 to 10.4 will be 
performed to evaluate and analyze safety information obtained in this study at an early stage 
and publish them as appropriate. 
 
11.0 
Posting of Information Regarding This Study 
Prior to the start of the study, Takeda Pharmaceutical Company Limited will register 
information regarding this study to the public website specified below. 
 
Japan Pharmaceutical Information Center-Clinical Trials Information 
 
ClinicalTrials.gov (a clinical trial registration system provided by the National Institutes of Health) 
 
12.0 
Organizational Structure 
12.1 Person responsible for administration 
 
  
 Takeda Pharmaceutical Company Limited 
 
PPD

 
12 
12.2 Proper Use Committee 
The committee will provide advice on the protocol, data analysis, publication of study results, 
promotion of the proper use of Adcetris, and safety measures. 
(Listed in the order of the Japanese syllabary) 
 
12.3 Central Enrollment Center 
 
 
13.0 
Contract Research Organization 
 
14.0 
Other Important Information 
14.1 Protocol amendment 
During the study, the sponsor will monitor the occurrence of adverse drug reactions and 
serious adverse drug reactions that cannot be predicted by the progress of the study and 
precautions for use, the presence/absence of an increase in the frequency of specific adverse 
drug reactions, and the appropriateness of outcome measures, and review and amend this 
protocol as appropriate. If the approval of partial changes to “Dosage and Administration” or 
“Indication” is obtained during the study, the sponsor will consider the necessity of 
amendment of this protocol as appropriate, and amend the protocol as appropriate. 
 
14.2 Measures to be taken in response to issues/questions 
If any safety and/or efficacy issue is detected, the sponsor will examine data closely and 
consider what measures should be taken. 
 
 
 
PPD
PPD
PPD

 
13 
Time point 
 
 
Procedure 
Observation period 
At the time 
of patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Patient enrollment 
Date of the expected initial dose of Adcetris 
○ 
 
 
 
 
Patient identification number 
○ 
Patient initial 
○ 
 
Sex 
○ 
Date of birth 
○ 
Diagnosis 
○ 
Performance status 
○ 
 
 
 
CD30 
○ 
 
 
 
Past history of severe hypersensitivity to any 
ingredient of Adcetris 
○ 
 
 
 
Expected concomitant use of other 
antineoplastic drugs 
○ 
 
 
 
Presence/absence of infections 
○ 
 
 
 
 
Presence/absence of peripheral nerve 
disorders 
○ 
 
 
 
Presence/absence of hepatic disorders 
○ 
 
 
 
Presence/absence of severe renal disorders 
○ 
 
 
 
Presence/absence of pregnancy/breast-feeding 
○ 
 
 
 
Patient demographics and baseline characteristics 
Date of diagnosis of Hodgkin or anaplastic 
large-cell lymphoma 
○ 
 
 
Site of involvement 
○ 
 
 
ALK (in patients with anaplastic large cell 
lymphoma) 
○ 
 
 
Clinical stage 
○ 
 
 
Presence/absence of B symptoms 
○ 
 
 
ECOG Performance Status 
 
○ 
 
 
 
Therapeutic category 
 
○ 
 
 
Hypersensitivity disposition 
 
○ 
 
 
Viral test results 
 
○ 
 
 
Past history of and concurrent pulmonary 
disorders 
 
○ 
 
 
Past history of and concurrent malignant 
tumours 
 
○ 
 
 
Concurrent illness (other than pulmonary 
disorders and malignant tumours) 
 
○ 
 
 
Past history (other than pulmonary disorders 
and malignant tumours) 
 
○ 
 
 
 
Height and weight 
 
○ 
 
 
Smoking history 
 
○ 
 
 
Prior treatment for Hodgkin's or anaplastic 
large cell lymphoma 
 
○ 
 
 
 
Appendix 1 Study Schedule 

 
14 
 
 
         Time point 
 
 
   Procedure 
Observation period 
At the time of 
patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Treatment given 
Treatment with Adcetris 
 
○ 
○ 
 
 
Post-baseline hematopoietic stem cell 
transplantation 
 
○ 
○ 
Drug(s) other than Adcetris used for the 
treatment of the primary disease 
 
○ 
○ 
Drug(s) used for the prevention of infection 
 
○ 
○ 
Tests and assessments 
Laboratory tests (red blood cell count, 
hemoglobin level, white blood cell count, 
neutrophil count, lymphocyte count, platelet 
count, and liver and kidney function tests) 
 
 
○ 
○ 
Best response 
 
 
○ 
○ 
Date of the final observation 
 
 
 
○ 
○ 
Presence/absence of pregnancy (for females 
only) 
 
○ 
○ 
Adverse events 
 
○ 
○ 
 ○   : Data collected 
 ○   : Data collected throughout the period 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 2 Best Response Assessment Criteria (Revised Response Criteria for Malignant Lymphoma*)  
* Extracted from “General Rules for the Clinical and Pathological Studies on Tumors of Hematopoietic and 
Lymphoid Tissues, March 2000 [First Edition]) 

 
15 
For patients with PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
 The patient is PET negative. If the patient is PET negative, any residual tumor on CT does not matter. 
1)-2Variably FDG-avid lymphoma 
 The patient did not undergo PET before treatment. If the patient was negative before treatment, the patient 
must meet all the following criteria: 
 [1] All nodal target lesions are normal. 
 [2] All extranodal target lesions have resolved. 
 [3] All nodal non-target lesions are normal. 
 [4] The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
 [5] All extranodal non-target lesions have resolved. 
2) A patient with bone marrow infiltration at baseline must be negative for bone marrow infiltration. A patient 
with no bone marrow infiltration at baseline should be regarded as “negative” because bone marrow test is 
not required. 
3) The patient has no new lesion. 
PR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
If the patient had one or more PET positive lesions, or was PET negative AND had bone marrow infiltration 
at baseline, the patient must be positive for bone marrow infiltration at the time of restaging (or have not 
undergone testing). 
1)-2Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
3) All nodal non-target lesions are normal or free from enlargement. 
4) All extranodal non-target lesions have resolved or free from enlargement. 
5) Bone marrow infiltration does not matter. Testing is not required. 
6) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR but meets any of the criteria 1 and 2 to 6 and 7 listed below, the 
patient will be assessed as having progressive disease (PD). If the patient meets any of the criteria listed below 
after being assessed as achieving CR, the patient will be assessed as having a relapsed disease (RD): 
1)-1 Routinely FDG-avid lymphoma 
 The patient has one or more PET positive lesions. 
1)-2 Variably FDG-avid lymphoma 
 If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
3) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 
diameter) or re-enlargement. 
4) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
5) The long diameter of the nodal target lesion which was once normalized and assessed as CR exceeded 1.5 

 
16 
cm. The extranodal target lesion which once resolved reappeared. 
6) The patient has a new lesion. 
7) The patient became positive after being once negative for bone marrow infiltration. 
 
 
For patients with no PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
5) All extranodal non-target lesions have resolved. 
6) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
7) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
8) A patient with bone marrow infiltration or indeterminate at baseline must be negative for bone marrow 
infiltration. 
 A patient with no bone marrow infiltration at baseline should be regarded as “negative” because bone 
marrow test is not required. 
9) The patient has no new lesion. 
CRu   
The patient had bone marrow infiltration or was indeterminate at baseline AND meets all the following 
criteria: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) All extranodal non-target lesions have resolved. 
5) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
6) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
7) The patient is indeterminate for bone marrow infiltration. 
8) The patient has no new lesion. 
 
OR 
1) The patient has a 75% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal. 
3) All extranodal non-target lesions have resolved. 
4) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
5) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
6) The patient has no bone marrow infiltration or indeterminate. 
7) The patient has no new lesion. 
PR 
The patient meets all the above criteria for CRu except for criterion 6. A patient with bone marrow infiltration 
or indeterminate at baseline must be positive for bone marrow infiltration at the time of restaging. 
Or, the patient meets all the following criteria: 

 
17 
1) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal or free from enlargement. 
3) All extranodal non-target lesions have resolved or free from enlargement. 
4) Enlarged liver, spleen, and kidneys have resolved or are free from progression. 
5) All tumor-related symptom (fever and night sweat) have resolved. AND abnormal tumor-related laboratory 
test results (tumor-related increase in LDH) became normal. 
6) Bone marrow infiltration does not matter. Testing is not required. 
7) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR or CRu but meets any of the criteria below, the patient will be 
assessed as having progressive disease (PD). If the patient meets any of the criteria listed below after being 
assessed as achieving CR or CRu, the patient will be assessed as having a relapsed disease (RD): 
1) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
2) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 
diameter) or re-enlargement. 
3) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
4) The extranodal target lesion which once resolved and was assesses as CR or CRu reappeared. 
5) Obvious progression or recurrence of enlarged liver, spleen, or kidney. 
6) Obvious progression or recurrence of tumor-related subjective and objective symptoms (fever and night 
sweat) or abnormal tumor-related laboratory test results (tumor-related increase in LDH). 
7) The patient became positive after being once negative for bone marrow infiltration. 
8) The patient has a new lesion. 
 
 
 

 
 
 
 
 
Special Drug Use Surveillance Protocol 
Special Drug Use Surveillance of Adcetris IV Infusion 
(All-Case Surveillance) 
“Relapsed or Refractory CD30+ Hodgkin's Lymphoma 
or Anaplastic Large Cell Lymphoma” 
 
 
 
 
 
 
 
 
Version number 
Initial 
Date of creation 
January 17, 2014 
Sponsor 
Takeda Pharmaceutical Company Limited 
 

 
Table of Contents 
1.0 
Background ..................................................................................................................................... 1 
2.0 
Purpose ............................................................................................................................................ 1 
3.0 
Estimated Enrollment and Its Rationale ...................................................................................... 1 
3.1 
Estimated enrollment ................................................................................................................. 1 
3.2 
Rationale ...................................................................................................................................... 1 
4.0 
Eligible Patients ............................................................................................................................. 1 
5.0 
Dosage Regimen .............................................................................................................................. 2 
6.0 
Expected Study Institutions by Department ................................................................................ 2 
7.0 
Methods ........................................................................................................................................... 2 
7.1 
Observation period ...................................................................................................................... 2 
7.2 
Request for participation in this study and contract with each study institution ................. 2 
7.3 
Method of patient enrollment..................................................................................................... 3 
7.4 
Completion and submission of the case report form ................................................................ 4 
7.5 
Confirmation of all-case surveillance ........................................................................................ 4 
8.0 
Estimated Study Period ................................................................................................................. 4 
9.0 
Outcome Measures ......................................................................................................................... 5 
9.1 
Data to be recorded in Patient Enrollment Form ..................................................................... 5 
9.2 
Data to be recorded in Case Report Form ................................................................................. 5 
 
Cover sheet of Case Report Form ....................................................................................... 5 
9.2.1
 
Patient demographics and baseline characteristics .......................................................... 5 
9.2.2
 
Treatment given ................................................................................................................... 5 
9.2.3
 
Tests and assessments ......................................................................................................... 6 
9.2.4
 
Laboratory tests ............................................................................................................... 6 
9.2.4.1
 
Best response .................................................................................................................... 6 
9.2.4.2
 
Date of the final observation ........................................................................................... 6 
9.2.4.3
 
Other assessments ........................................................................................................... 6 
9.2.4.4
 
Adverse events ..................................................................................................................... 7 
9.2.5
10.0 Data to Be Analyzed and Methods of Analysis ........................................................................... 10 
10.1 Patient disposition .................................................................................................................... 10 
10.2 Patient demographics and baseline characteristics ............................................................... 10 
10.3 Treatment given ........................................................................................................................ 10 
10.4 Safety ......................................................................................................................................... 10 
 
Occurrence of adverse events ............................................................................................ 10 
10.4.1
 
Factors that may affect the safety of Adcetris ................................................................. 11 
10.4.2
 
Changes in laboratory test data over time ...................................................................... 11 
10.4.3
10.5 Efficacy ....................................................................................................................................... 11 
 
Best response ..................................................................................................................... 11 
10.5.1
 
Overall survival ................................................................................................................. 11 
10.5.2
10.6 Interim analyses ....................................................................................................................... 11 

 
11.0 
Posting of Information Regarding This Study ............................................................................ 11 
12.0 Organizational Structure ............................................................................................................. 11 
12.1 Person responsible for administration .................................................................................... 11 
12.2 Proper Use Committee .............................................................................................................. 11 
12.3 Central Enrollment Center ...................................................................................................... 12 
13.0 Contract Research Organization ................................................................................................. 12 
14.0 Other Important Information ...................................................................................................... 12 
14.1 Protocol amendment ................................................................................................................. 12 
14.2 Measures to be taken in response to issues/questions ........................................................... 12 
 
Appendices 
   Appendix 1 Study Schedule................................................................................................................................ 13 
   Appendix 2 Best Response Assessment Criteria................................................................................................. 15 
 

 
1 
1.0 
Background 
There is limited safety information on Adcetris IV Infusion 50 mg (hereinafter referred to as 
Adcetris) collected from Japanese patients in Japanese phase 1/2 studies. It is important to 
promptly collect post-marketing safety information and provide it to healthcare providers. It 
was also deemed that additional surveillance was required to determine the occurrence of 
peripheral nerve disorders, infections, neutropenia, infusion reactions, and pulmonary 
disorders in patients using Adcetris in Japan as post-marketing safety specifications. 
Thus, an all-case surveillance in all patients receiving treatment with Adcetris will be initiated 
as an additional pharmacovigilance activity for Adcetris when the drug is launched. 
This surveillance study will be conducted in compliance with the GPSP Ordinance and other 
related regulatory requirements. 
 
2.0 
Purpose 
The purpose of this study is to evaluate the safety of Adcetris in patients with 
relapsed/refractoryCD30+ Hodgkin's lymphoma or anaplastic large cell lymphoma in the 
routine clinical setting, as well as to collect efficacy information for reference. 
 
3.0 
Estimated Enrollment and Its Rationale 
3.1 Estimated enrollment  
140 patients (with relapsed/refractory CD30+ Hodgkin's lymphoma or anaplastic large cell 
lymphoma) 
 
3.2 Rationale 
It is expected that the detailed evaluation of peripheral nerve disorders, infections, neutropenia, 
infusion reactions, and pulmonary disorders will help better understand the safety profile of 
Adcetris in the routine clinical setting, which will lead to the assessment of the risk-benefit 
balance of the drug. 
The frequencies of peripheral nerve disorders, infections, neutropenia (≥Grade 3), infusion 
reaction, and pulmonary disorder in non-Japanese phase 2 studies (pooled study data from a 
study in patients with Hodgkin's lymphoma [SG035-0003, 102 patients] and a study in 
patients with systemic anaplastic large cell lymphoma [SG035-0004, 58 patients]) were 56%, 
61%, 20%, 11%, and 6%, respectively. 
Observation of infusion reactions with the lowest frequency of ≥10 patients, aside from 
pulmonary disorders, with a probability of 95% would require 140 patients, which was 
therefore determined to be the estimated enrollment. It is estimated that when the number of 
patients enrolled reaches 140 patients, ≥4 patients have adverse events of pulmonary disorder 
with a probability of 95%. 
 
4.0 
Eligible Patients 
All patients receiving treatment with Adcetris 

 
2 
 
5.0 
Dosage Regimen 
The usual adult dosage is 1.8 mg/kg (body weight) of brentuximab vedotin (recombinant) 
infused intravenously once every three weeks. The dose should be adjusted depending on the 
patient's condition. 
See the "PRECAUTIONS" section of the package insert. 
 
6.0 
Expected Study Institutions by Department 
The study will be conducted at all institutions using Adcetris (e.g., department of hematology) 
(approximately 100 study institutions are expected to participate in the study). 
 
7.0 
Methods 
7.1 Observation period 
From the start of treatment with Adcetris until the completion of 16 cycles [3 weeks per cycle] 
 
* Rationale for the selection of the observation period 
The assessment of the treatment cycle with the initial onset of adverse events in a clinical 
study [SGN35-006, the extended treatment group] evaluating the safety of Adcetris after Cycle 
17 showed a tendency that most adverse events occurred before Cycle 16. In addition, the 
types and severities did not differ between adverse events occurring after Cycle 17 and those 
occurring before Cycle 16. This suggested that the safety profile of Adcetris would be 
generally determined before Cycle 16. Therefore, the observation period was defined as the 
period from the start of treatment with Adcetris until the completion of 16 cycles. 
 
7.2 Request for participation in this study and contract with each study institution 
Paper-based case report forms will be used. To ask each study institution to participate in the 
study, the medical representative of Takeda Pharmaceutical Company Limited (Takeda MR) 
will confirm before supply of Adcetris and the start of the study that each study institution 
meets all requirements for study institutions and investigators specified below, and have a 
written contract with the study institution after prior explanation of the study provided before 
supply of Adcetris. 
 
(1) Requirements for each study institution and investigator 
1) Requirements for each study institution 
[1] Is able to cooperate with this all-case surveillance and have a contract with the 
sponsor. 
[2] Is able to provide specialized treatment for hematopoietic tumors. 
[3] Is able to provide emergency treatment if required (including a case where such a 
treatment can be provided in conjunction with another institution 
). 

 
3 
* When emergency treatment is provided in conjunction with another institution, 
information on Adcetris safety measures and treatment of adverse drug reactions should 
be shared between the institution and the other institution to build a coalition. 
 
2) Requirements for each investigator 
[1] Has adequate knowledge and experience regarding the treatment of hematopoietic 
tumors, or is under the direction of a healthcare professional having such knowledge 
and experience. 
[2] Is able to cooperate with this all-case surveillance. 
 
 
(2) Prior explanation of the study to be provided before supply of Adcetris and the request for 
participation in this study 
Using “Request for Participation in the Special Drug Use Surveillance,” “Study Outline,” 
“Patient Enrollment Form (sample),” “Case Report Form Parts 1 and 2 (sample),” 
“Precautions for Use/Instruction Manual,” and “Proper Usage Guide,” the Takeda MR will 
explain the purpose and methods (e.g., all-case surveillance) of this survey study and 
information regarding the proper use of Adcetris to the investigator and ask him/her to 
participate in the all-case surveillance. 
The Takeda MR will also confirm with the investigator that the institution and the 
investigator meet all requirements. 
 
(3) Request for participation in this study and contract with each study institution 
The Takeda MR will have a written contract with the study institution after obtaining their 
agreement to participate in this study Takeda Pharmaceutical Company Limited will inform 
the outsourced Adcetris supplier that the contract is concluded and Adcetris should be 
supplied to the study institution. The Takeda MR will deliver patient enrollment forms to the 
investigator. 
 
7.3 Method of patient enrollment 
The central enrollment method via FAX will be used. For each patient scheduled to receive 
treatment with Adcetris after the date of the start of the term of the contract with the study 
institution, the investigator will complete patient enrollment by submitting the Patient 
Enrollment Form with information required for patient enrollment filled in (see Section 9.1) 
via FAX to the Central Enrollment Center (see Section 12.3) until noon of the day before the 
date of the expected initial dose of Adcetris. 
The Central Enrollment Center will review the Patient Enrollment Form and send the 
Enrollment Completion Notice to the investigator via FAX. After receiving the Enrollment 
Completion Notice, the investigator will initiate treatment with Adcetris. 
 

 
4 
The Case Report Form consists of Parts 1 and 2 per patient. 
The Takeda MR will deliver Case Report Form Part 1, which is issued after enrollment 
confirmation by the Central Enrollment Center, to the investigator. Case Report Form Part 2 is 
issued after the completion of follow-up on Case Report Form Part 1. 
 
7.4 Completion and submission of the case report form 
For all patients requiring the completion of the case report form, the investigator will complete 
the case report form during the period from the start of treatment with Adcetris until the end of 
Cycle 4 and within 1 month after the end of Cycle 16, and submit it to the Takeda MR. 
If treatment with Adcetris is discontinued for any reason before the end of the observation 
period, the investigator will complete the case report form within 1 month after the completion 
of required observation submit it to the Takeda MR. If treatment with Adcetris is discontinued 
due to any adverse event, however, the investigator will continue to observe the patient after 
treatment discontinuation until the adverse event resolves or improves wherever possible, and 
then complete the case report form and submit it to the Takeda MR. 
 
7.5 Confirmation of all-case surveillance 
After the completion of the study, the principal investigator will confirm that case report forms 
of all patients treated with Adcetris have been submitted, and sign or fill in his/her name with 
seal on All-Case Surveillance Confirmation Form and submit it to the Takeda MR. 
 
8.0 
Estimated Study Period 
Study period: Starts on the day of the launch of Adcetris (April, 2014) and ends once the 
all-case surveillance is no longer a condition for approval of the product. 
Patient enrollment period: Starts on the day of the launch of Adcetris (April, 2014) and ends 
once the all-case surveillance is no longer a condition for approval of the 
product. 
 
Once it is predicted exactly when the estimated number of enrolled patients will be achieved, 
the sponsor will discuss with Pharmaceuticals and Medical Devices Agency to determine 
when to move to the period only requiring patient enrollment (not requiring the completion 
and submission of case report forms) from the period requiring the completion and submission 
of case report forms, after confirming that required data will be available based on enrollment 
status and the progress of the collection of case report forms. 
It is expected that the number of enrolled patients will reach 140 in September 2015. 
 
* Rationale for the expectation 
It was expected that the estimated number of enrolled patients (140) would be achieved in 
September 2015 (1 year and 6 months after the expected date of launch) based on the 
estimated number of patients treated with Adcetris during the post-marketing period 

 
5 
(approximately 100 person/years). 
 
9.0 
Outcome Measures 
The investigator will record data listed below in both Patient Enrollment and Case Report 
Forms. Study schedule is provided in in Appendix 1. 
9.1 Data to be recorded in Patient Enrollment Form 
1) Outcome measures 
Name of the institution, name of the investigator completing Patient Enrollment Form, 
expected date of the start of treatment with Adcetris, patient identification number, patient 
initial, sex, date of birth, diagnosis, performance status, CD30, past history of severe 
hypersensitivity to any ingredient of Adcetris, expected concomitant use of other 
antineoplastic drugs, and presence/absence of infections, peripheral nerve disorders, hepatic 
disorders, severe renal disorders, or pregnancy/breast-feeding 
2) When to collect outcome measure data 
At the time of patient enrollment 
 
9.2 Data to be recorded in Case Report Form 
 Cover sheet of Case Report Form 
9.2.1
Date of the finial completion of Case Report Form and name of the investigator completing 
Case Report Form 
 
 Patient demographics and baseline characteristics 
9.2.2
1) Outcome measures 
Date of diagnosis of Hodgkin's or anaplastic large cell lymphoma, site of involvement, 
ALK (in patients with anaplastic large cell lymphoma), clinical stage, presence/absence of 
B symptoms, ECOG Performance Status, therapeutic category, (presence/absence and 
detail of) hypersensitivity disposition, viral test results, past history of and concurrent 
pulmonary disorders, past history of and concurrent malignant tumours, (presence/absence 
and detail of) concurrent illnesses [other than pulmonary disorders and malignant tumours], 
(presence/absence and detail of) past history[other than pulmonary disorders and malignant 
tumours], height, weight, smoking history, and (presence/absence and detail of) prior 
treatment for Hodgkin's lymphoma or anaplastic large cell lymphoma (including drug 
therapy, radiotherapy, and hematopoietic stem cell transplantation) 
2) When to collect outcome measure data 
At the start of treatment with Adcetris 
 
 Treatment given 
9.2.3
1) Outcome measures 
Treatment with Adcetris and premedication to prevent infusion reaction (dose, date of 
premedication, and reasons for premedication to prevent infusion reaction and its 

 
6 
discontinuation), (use or non-use, type, and date of) post-baseline hematopoietic stem cell 
transplantation, (presence/absence, name, and duration of) drugs other than Adcetris used 
for the treatment of the primary disease, and (presence/absence, name, and duration of) 
drugs used for the prevention of infection 
2) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Tests and assessments 
9.2.4
 Laboratory tests 
9.2.4.1
1) Outcome measures 
Red blood cell count, hemoglobin level, white blood cell count, neutrophil count, 
lymphocyte count, platelet count, total bilirubin, AST, ALT, LDH, BUN, and serum 
creatinine 
2) When to collect outcome measure data 
At each test time point during the period from the start of treatment with Adcetris until the 
completion of 16 cycles (or upon discontinuation of treatment with Adcetris) 
 
 Best response 
9.2.4.2
1) Outcome measures 
The best response (CR, CRu [for patients with no PET scan data], PR, SD, or PD) will be 
assessed based on CT and PET scans of the neck, chest, abdomen, and pelvis according to 
the best response assessment criteria (see Appendix). 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Date of the final observation 
9.2.4.3
1) Outcome measures 
Date of the final observation 
2) When to collect outcome measure data 
After 16 cycles of treatment with Adcetris (or upon discontinuation of treatment with 
Adcetris) 
 
 Other assessments 
9.2.4.4
1) Outcome measures 
Pregnancy during the observation period (for females only) 
If pregnancy is detected during the observation period, it should be reported to the Takeda 
MR immediately. 
2) When to collect outcome measure data 

 
7 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 Adverse events 
9.2.5
1) Outcome measures 
Presence/absence of adverse events (see Table 1), adverse event terms, date of onset, 
CTCAE grade (the worst one), seriousness and its reason (see Table 2), (presence/absence 
and detail of) action taken to Adcetris, (presence/absence and detail of) intervention for 
adverse events, date of outcome, outcome, causal relationship with Adcetris* (see Table 3), 
and changes in laboratory test values associated with adverse events over time 
If the outcome is “not recovered/not resolved” or “unknown,” and the causal relationship 
with Adcetris is considered unevaluable, the event should be followed wherever possible. 
* If the event is considered not related to Adcetris, its rationale should be collected. If the causal 
relationship with Adcetris is considered unevaluable, its reason should be collected. 
Note) Points to consider regarding adverse events 
Worsening of the primary disease should not be regarded as an adverse event. However, abnormal 
worsening of the primary disease (e.g., worsening beyond the expected natural course of the 
disease) should be regarded as an adverse event. 
Disease progression should be regarded as worsening of the primary disease rather than an adverse 
event. However, clinical or laboratory progression of an existing cancer (including new metastasis) 
that meets any of the criteria for the seriousness of adverse events (see Table 2) should be 
considered a serious adverse event. 
2) Adverse events of particular interest 
The events listed below are events of particular interest; detailed information on these 
events should be collected wherever possible it they are observed:  
• Peripheral nerve disorders 
• Infections 
• Neutropenia 
• Infusion reactions 
• Pulmonary disorders 
 
* Rationale for the selection of adverse events of particular interest 
Of important identified risks listed in Risk Management Plan, those listed above were 
selected as adverse events of particular interest based on the following rationales: 
a) Peripheral nerve disorders 
Peripheral nerve disorders are frequently observed after treatment with Adcetris. If the 
event of peripheral nerve disorder becomes severe, it is difficult to continue treatment 
with Adcetris. It is important to control the onset of the event to allow for continuation of 
treatment (including dose reduction and restart of treatment after treatment interruption). 

 
8 
Therefore, the profile of peripheral nerve disorders in Japanese patients as an adverse 
event of particular interest will be determined (i.e., information useful for continuation of 
treatment with Adcetris, including risk factors, commonly reported time to onset, 
outcomes, and the status of treatment with Adcetris, will be collected). 
b) Infections 
It is expected that Adcetris is used in patients who are immunocompromised due to prior 
treatment or the prior disease or those who are complicated with infection, and the 
incidence of infections is likely to be high. Therefore, the profile of infections in Japanese 
patients as an adverse event of particular interest (i.e., the incidence and temporal 
relationship with the onset of neutropenia/lymphopenia) will be determined. 
c) Neutropenia 
It is expected that Adcetris is used in patients with decreased neutrophil count due to prior 
treatment, which may increase the risk of infection and result in a high incidence of 
infection/severe infection. It is important to control the neutrophil count to allow for 
continuation of treatment (including dose reduction and restart of treatment after 
treatment interruption) in terms of the prevention of infection. Therefore, the profile of 
neutropenia in Japanese patients as an adverse event of particular interest will be 
determined (i.e., the status of treatment with Adcetris and neutrophil count control will be 
assessed and information useful for continuation of treatment with Adcetris will be 
collected). 
d) Infusion reactions  
Infusion reactions are characteristic of monoclonal antibody preparations, the profile of 
infusion reactions in Japanese patients as an adverse event of particular interest (including 
the status of premedication and the percentage of patients using premedication to prevent 
infusion reactions [use/non-use of premedication to prevent infusion reactions]) will be 
determined. 
e) Pulmonary disorders 
The occurrence of pulmonary disorders in Japanese patients receiving monotherapy with 
Adcetris as an adverse event of particular interest will be determined. 
3) When to collect outcome measure data 
From the start of treatment with Adcetris until the completion of 16 cycles (or upon 
discontinuation of treatment with Adcetris) 
 
 

 
9 
Table 1 Definition of an Adverse Event 
An adverse event (AE) is any untoward or undesirable medical occurrence in a patient linked in time 
with the use of a pharmaceutical/ medicinal product and which does not necessarily have to have a 
causal relationship with this treatment or may or may not be considered related to the product. 
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not related to the medicinal product. 
Adverse events also include: 
・Symptoms observed in an infant breast-fed by a mother receiving treatment with Adcetris. 
 
Table 2 Criteria for the Seriousness of Adverse Events 
An adverse event meeting any of the following criteria will be considered serious: 
1. Results in death. 
2. Is life-threatening. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization. 
4. Results in persistent or significant disability/incapacity. 
5. Is a congenital anomaly/birth defect. 
6. Is a medically important condition due to any of the above 1 to 5, including those listed in “Takeda 
Medically Significant AE List.” 
 
Takeda Medically Significant AE List 
•Acute respiratory failure/acute respiratory distress 
syndrome (ARDS) 
•Anaphylactic shock 
•Torsade de pointes/ventricular fibrillation/ventricular 
tachycardia 
•Acute kidney failure 
•Malignant hypertension 
•Pulmonary hypertension 
•Convulsive seizure (including convulsion and 
epilepsy) 
•Pulmonary fibrosis (including interstitial 
pneumonia) 
•Agranulocytosis 
•Neuroleptic malignant syndrome/malignant 
hyperthermia 
•Aplastic anemia 
•Spontaneous abortion/stillbirth and fetal 
death 
•Toxic epidermal necrolysis/oculomucocutaneous 
syndrome (Stevens-Johnson syndrome) 
•(Suspected) transmission of infection via a 
drug 
•Hepatic necrosis 
•(Suspected) endotoxic shock 
•Acute hepatic failure 
 
 

 
10 
Table 3 Criteria for the Assessment of Causal Relationship between Adverse Events and 
Adcetris 
Causality 
Assessment criterion 
Related 
There is a temporal relationship between the event and Adcetris (and 
the clinical course after treatment discontinuation). Or, there are other 
contributing factors, such as the primary disease, concurrent illnesses, 
and concomitant medications/therapies, but it is also likely that the 
event is attributable to Adcetris. 
Not related 
There is no temporal relationship between the event and Adcetris. Or, 
it is very likely that the event is attributable to other factors, such as 
the primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
Indeterminate 
There is limited information required for the assessment of causal 
relationship, such as temporal relationship between the event and 
Adcetris (and the clinical course after treatment discontinuation), the 
primary disease, concurrent illnesses, and concomitant 
medications/therapies. 
 
10.0 
Data to Be Analyzed and Methods of Analysis 
10.1 Patient disposition 
Data to be analyzed includes the number of enrolled patients, the number of patients whose 
case report forms are available, and the number of patients included in and excluded from the 
safety/efficacy analysisset and reasons for inclusion/exclusion. 
 
10.2 Patient demographics and baseline characteristics 
Data to be analyzed includes sex, age, disease duration, site of involvement, and clinical stage. 
 
10.3 Treatment given 
Data to be analyzed includes the status of treatment with Adcetris and concomitant 
medications. 
 
10.4 Safety 
The measures specified below will be analyzed using the safety analysis set. Adverse events 
will be coded using MedDRA/J and summarized using (Preferred Terms [PTs]) and System 
Organ Classes [SOCs]). 
 Occurrence of adverse events 
10.4.1
The frequency of adverse events observed during the observation period will be analyzed 
by type, time of onset, seriousness, and Adcetris. 
 

 
11 
 Factors that may affect the safety of Adcetris 
10.4.2
The frequency of adverse events observed during the observation period will be analyzed 
by patient background factors (sex, age, presence/absence of concurrent renal disorders, 
and presence/absence of concurrent hepatic disorders) and treatment given (the status of 
treatment with Adcetris and concomitant medications). 
 
 Changes in laboratory test data over time 
10.4.3
Summary statistics of laboratory test values at baseline and post-baseline will be calculated. 
 
10.5 Efficacy 
The measures specified below will be analyzed using the efficacy analysis set. 
 Best response 
10.5.1
The best response after 16 cycles of treatment with Adcetris (or upon discontinuation of 
treatment with Adcetris) will be analyzed. 
 
 Overall survival 
10.5.2
The time to death (regardless of the cause of death) will be analyzed using the “final 
observation date” in specified in Section 9.2.4.3 as the date of survival confirmation and the 
date of outcome of an adverse event with “Died/fetal” recorded in the Outcome field 
specified in Section 9.2.5 as the date of death 
 
10.6 Interim analyses 
For patients whose case report forms are collected through March 31, 2015 with evaluable 
safety evaluation, analyses similar to the ones described in Sections 10.1 to 10.4 will be 
performed to evaluate and analyze safety information obtained in this study at an early stage 
and publish them as appropriate. 
 
11.0 
Posting of Information Regarding This Study 
Prior to the start of the study, Takeda Pharmaceutical Company Limited will register 
information regarding this study to Clinical Trials.gov and a public website (JAPIC-CTI*). 
*Japan Pharmaceutical Center-Clinical Trials Information 
 
12.0 
Organizational Structure 
12.1 Person responsible for administration 
 
  
 Takeda Pharmaceutical Company Limited 
 
12.2 Proper Use Committee 
The committee will provide advice on the protocol, data analysis, publication of study results, 
PPD

 
12 
promotion of the proper use of Adcetris, and safety measures. 
(Listed in the order of the Japanese syllabary) 
 
12.3 Central Enrollment Center 
 
 
13.0 
Contract Research Organization 
 
14.0 
Other Important Information 
14.1 Protocol amendment 
During the study, the sponsor will monitor the occurrence of adverse drug reactions and 
serious adverse drug reactions that cannot be predicted by the progress of the study and 
precautions for use, the presence/absence of an increase in the frequency of specific adverse 
drug reactions, and the appropriateness of outcome measures, and review and amend this 
protocol as appropriate. If the approval of partial changes to “Dosage and Administration” or 
“Indication” is obtained during the study, the sponsor will consider the necessity of 
amendment of this protocol as appropriate, and amend the protocol as appropriate. 
 
14.2 Measures to be taken in response to issues/questions 
If any safety and/or efficacy issue is detected, the sponsor will examine data closely and 
consider what measures should be taken. 
 
 
 
PPD
PPD
PPD

 
13 
Time point 
 
 
Procedure 
Observation period 
At the time 
of patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuation 
of treatment 
Patient enrollment 
Date of the expected initial dose of Adcetris 
○ 
 
 
 
 
Patient identification number 
○ 
Patient initial 
○ 
 
Sex 
○ 
Date of birth 
○ 
Diagnosis 
○ 
Performance status 
○ 
 
 
 
CD30 
○ 
 
 
 
Past history of severe hypersensitivity to any 
ingredient of Adcetris 
○ 
 
 
 
Expected concomitant use of other 
antineoplastic drugs 
○ 
 
 
 
Presence/absence of infections 
○ 
 
 
 
 
Presence/absence of peripheral nerve 
disorders 
○ 
 
 
 
Presence/absence of hepatic disorders 
○ 
 
 
 
Presence/absence of severe renal disorders 
○ 
 
 
 
Presence/absence of pregnancy/breast-feeding 
○ 
 
 
 
Patient demographics and baseline characteristics 
Date of diagnosis of Hodgkin or anaplastic 
large-cell lymphoma 
○ 
 
 
Site of involvement 
○ 
 
 
ALK (in patients with anaplastic large cell 
lymphoma) 
○ 
 
 
Clinical stage 
○ 
 
 
Presence/absence of B symptoms 
○ 
 
 
ECOG Performance Status 
 
○ 
 
 
 
Therapeutic category 
 
○ 
 
 
Hypersensitivity disposition 
 
○ 
 
 
Viral test results 
 
○ 
 
 
Past history of and concurrent pulmonary 
disorders 
 
○ 
 
 
Past history of and concurrent malignant 
tumours 
 
○ 
 
 
Concurrent illness (other than pulmonary 
disorders and malignant tumours) 
 
○ 
 
 
Past history (other than pulmonary disorders 
and malignant tumours) 
 
○ 
 
 
 
Height and weight 
 
○ 
 
 
Smoking history 
 
○ 
 
 
Prior treatment for Hodgkin's or anaplastic 
large cell lymphoma 
 
○ 
 
 
 
Appendix 1 Study Schedule 

 
14 
 
 
         Time point 
 
 
   Procedure 
Observation period 
At the time of 
patient 
enrollment 
At the start of 
treatment 
with Adcetris 
During treatment 
After 16 
cycles 
 
Upon 
discontinuatio
n of treatment 
Treatment given 
Treatment with Adcetris 
 
○ 
○ 
 
 
Post-baseline hematopoietic stem cell 
transplantation 
 
○ 
○ 
Drug(s) other than Adcetris used for the 
treatment of the primary disease 
 
○ 
○ 
Drug(s) used for the prevention of infection 
 
○ 
○ 
Tests and assessments 
Laboratory tests (red blood cell count, 
hemoglobin level, white blood cell count, 
neutrophil count, lymphocyte count, platelet 
count, and liver and kidney function tests) 
 
 
○ 
○ 
Best response 
 
 
○ 
○ 
Date of the final observation 
 
 
 
○ 
○ 
Presence/absence of pregnancy (for females 
only) 
 
○ 
○ 
Adverse events 
 
○ 
○ 
 ○   : Data collected 
   ○   : Data collected throughout the period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 2 Best Response Assessment Criteria (Revised Response Criteria for Malignant Lymphoma*)  
* Extracted from “General Rules for the Clinical and Pathological Studies on Tumors of Hematopoietic and 
Lymphoid Tissues, March 2000 [First Edition]) 
For patients with PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
The patient is PET negative. If the patient is PET negative, any residual tumor on CT does not matter. 
1)-2Variably FDG-avid lymphoma 
The patient did not undergo PET before treatment. If the patient was negative before treatment, the patient 
must meet all the following criteria: 
[1] All nodal target lesions are normal. 
[2] All extranodal target lesions have resolved. 
[3] All nodal non-target lesions are normal. 
[4] The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
[5] All extranodal non-target lesions have resolved. 
2) A patient with bone marrow infiltration at baseline must be negative for bone marrow infiltration. A patient 
with no bone marrow infiltration at baseline should be regarded as “negative” because bone marrow test is 
not required. 
3) The patient has no new lesion. 
PR 
All the following criteria are met: 
1)-1 Routinely FDG-avid lymphoma 
If the patient had one or more PET positive lesions, or was PET negative AND had bone marrow infiltration 
at baseline, the patient must be positive for bone marrow infiltration at the time of restaging (or have not 
undergone testing). 
1)-2Variably FDG-avid lymphoma 
If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
3) All nodal non-target lesions are normal or free from enlargement. 
4) All extranodal non-target lesions have resolved or free from enlargement. 
5) Bone marrow infiltration does not matter. Testing is not required. 
6) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR but meets any of the criteria 1 and 2 to 6 and 7 listed below, the 
patient will be assessed as having progressive disease (PD). If the patient meets any of the criteria listed below 
after being assessed as achieving CR, the patient will be assessed as having a relapsed disease (RD): 
1)-1 Routinely FDG-avid lymphoma 
The patient has one or more PET positive lesions. 
1)-2 Variably FDG-avid lymphoma 
If the patient did not undergo a PET scan or was PET negative prior to treatment, no PET assessment should 
be performed. 
2) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
3) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 

 
16 
diameter) or re-enlargement. 
4) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
5) The long diameter of the nodal target lesion which was once normalized and assessed as CR exceeded 1.5 
cm. The extranodal target lesion which once resolved reappeared. 
6) The patient has a new lesion. 
7) The patient became positive after being once negative for bone marrow infiltration. 
 
 
For patients with no PET scan data available 
Assessment 
Criteria 
CR 
All the following criteria are met: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) The image shows the resolution of all nodal lesions in all organs including the spleen and the liver. 
5) All extranodal non-target lesions have resolved. 
6) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
7) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
8) A patient with bone marrow infiltration or indeterminate at baseline must be negative for bone marrow 
infiltration. 
A patient with no bone marrow infiltration at baseline should be regarded as “negative” because bone marrow 
test is not required. 
9) The patient has no new lesion. 
CRu 
The patient had bone marrow infiltration or was indeterminate at baseline AND meets all the following 
criteria: 
1) All nodal target lesions are normal. 
2) All extranodal target lesions have resolved. 
3) All nodal non-target lesions are normal. 
4) All extranodal non-target lesions have resolved. 
5) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
6) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
7) The patient is indeterminate for bone marrow infiltration. 
8) The patient has no new lesion. 
 
OR 
1) The patient has a 75% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal. 
3) All extranodal non-target lesions have resolved. 
4) There is no enlarged liver, spleen, or kidney (all lesions have resolved). 
5) There is no tumor-related symptom (fever and night sweat) (all symptom have resolved) OR no abnormal 
tumor-related laboratory test results (tumor-related increase in LDH) (normal). 
6) The patient has no bone marrow infiltration or indeterminate. 

 
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7) The patient has no new lesion. 
PR 
The patient meets all the above criteria for CRu except for criterion 6. A patient with bone marrow infiltration 
or indeterminate at baseline must be positive for bone marrow infiltration at the time of restaging. 
Or, the patient meets all the following criteria: 
1) The patient has a 50% or more decrease (reduction) in the SPD of target lesion from baseline. 
2) All nodal non-target lesions are normal or free from enlargement. 
3) All extranodal non-target lesions have resolved or free from enlargement. 
4) Enlarged liver, spleen, and kidneys have resolved or are free from progression. 
5) All tumor-related symptom (fever and night sweat) have resolved. AND abnormal tumor-related laboratory 
test results (tumor-related increase in LDH) became normal. 
6) Bone marrow infiltration does not matter. Testing is not required. 
7) The patient has no new lesion. 
SD 
The patient achieved a response of <PR and >PD. 
PD 
If the patient is not assessed as achieving CR or CRu but meets any of the criteria below, the patient will be 
assessed as having progressive disease (PD). If the patient meets any of the criteria listed below after being 
assessed as achieving CR or CRu, the patient will be assessed as having a relapsed disease (RD): 
1) The patient has a 50% or more increase in the SPD of target lesion from the minimum SPD. 
2) The patient has an obvious increase in the nodal non-target lesion (a 50% or more increase in the long 
diameter) or re-enlargement. 
3) The patient has an obvious increase in the extranodal non-target lesion (a 50% or more increase in the long 
diameter) or recurrence. 
4) The extranodal target lesion which once resolved and was assesses as CR or CRu reappeared. 
5) Obvious progression or recurrence of enlarged liver, spleen, or kidney. 
6) Obvious progression or recurrence of tumor-related subjective and objective symptoms (fever and night 
sweat) or abnormal tumor-related laboratory test results (tumor-related increase in LDH). 
7) The patient became positive after being once negative for bone marrow infiltration. 
8) The patient has a new lesion.