NORTHEASTERN UNIVERSITY

Informed Consent Form

Writing Assignment # 1

Tosha Dave & Sonia Martorano

5/4/2015

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Kyowa Hakko Kirin Pharma, Inc.

INCFORMED CONSENT TO PARTICIPATE IN CLINICAL RESEARCH

Study: A Study of KW-2478 in Combination with Bortezomib in Subjects with

Relapsed and/ or Refractory Multiple Myeloma

Study Director: Michael Kurman, MD

Study Chair: Loan Hoang- Sayag, MD

Study Chair: Noel Pingoy, MD

Phone No. (201) 510-9766

Phone No. (201) 217-4631

Phone No. (201) 268-4031

SUBJECT CODE: _______________________________

INTRODUCTION

Through this document, we give you an invitation to participate voluntarily in a clinical research

study. You are being invited in this study because you have been diagnosed with Multiple

Myeloma. This study aims to assess the safety and benefits of the investigational study drug, KW-

2478, when given with Bortezomib (Velcade®).

Before you agree to participate in this study, you are presented herein called "Informed Consent",

which will provide you with the information regarding the purpose of study, study procedures,

what you are expected to do, what benefits you will get and what are possible risks to your health

from the participation.

Please read this form carefully. You can discuss this research study with your family members,

friends and your primary care physician, if necessary. If you have any questions feel free to ask

us. You can also call the Research Study Helpline number (201) 350-3500 for questions. If you

have questions, during your participation, you can ask them directly to your treating doctor/

investigator.

Your participation in the research study is completely voluntary. You can decide not to participate

or if you do, you can change your mind later on to end your participation. There will be no penalty

and you will not lose any benefits you receive now or entitled to receive. You are free to withdraw

from this research study at any time. However, you must return to see the doctor of the study for

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safety reasons. Thereby, you can be removed from the investigation and referred to follow-up care

(end of treatment procedures / withdrawal).

You CAN ONLY take part in this research if:

You are diagnosed with Multiple Myeloma.

You are older than 18 years of age.

You did not feel better after getting other available treatments for Multiple Myeloma.

You are able to take care of yourself and not confined to bed.

You may/may not be able to perform work activities more than 50% of the total time you

are awake.

You do not have any other serious illness besides Multiple Myeloma.

You have signs of end organ failure (such as traces protein in urine or serum).

If you are a male, you are willing to use condoms every time you are involved in sexual

activity starting with your participation until two months following your participation.

If you are a female and have potential to become pregnant, you are willing to use effective

form of contraception starting from at least a month before you participate until after two

months following your participation in research study.

You CANNOT take part in this research study if:

You have other severe illnesses.

You have not taken any other treatment for Multiple Myeloma in past four weeks.

You have not taken Bortezomib (name of medication) in last two months.

You have not taken any therapy that can suppress your immune system.

If you are woman who is pregnant or breastfeeding or want to be pregnant soon.

Besides the criteria mentioned above, there will be additional screening test (discussed in

details on page 4, 5 and 6 of this form) done. That is to make sure whether you are eligible

to participate in the research study.

Once you decide to participate, you will be asked to sign this form. You can take your time to

think and sign it. You can submit it to the facility later. You will get a copy of signed form for

your future reference.

NOTE: If you are a patient of Multiple Myeloma and NOT eligible to participate in the study but

yet interested in getting investigational drug (KW-2478), you may contact Michael Kurman, Study

Director at (201) 510-9766. He will guide you further.

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INVOLUNTARY TERMINATION OF YOUR PARTICIPATION

Once the research study begins, your wellbeing is company’s prime responsibility. The study

doctor or the study sponsor has authority to end your participation from the study without your

consent if:

The study doctor decides that the study is causing harm to your health.

The study is interrupted by the study sponsor, the Institutional Review Board (IRB) or

Independent Ethics Committee (IEC- a group of people who review the research to protect

your rights) or by the regulatory agency to protect your rights, health and welfare.

You do not follow the instructions of the study team.

If that happens, the investigator will follow-up with you for end of treatment procedures.

PURPOSE OF THE STUDY

The purpose of this study is to evaluate the safety and benefits of the investigational study drug

named KW-2478 when given with Bortezomib (Velcade®).

Bortezomib is a drug approved for the treatment of Multiple Myeloma (MM) on June 28, 2008 by

FDA. Multiple Myeloma is a type of cancer in which plasma cells (White blood cells) produce

abnormal proteins causing kidney problems. The KW-2478 is investigational drug whose safety

and benefits will be studied through this research study.

The study will take place in two different parts: Phase I and Phase II. The second part (Phase II)

of the study will begin only after successful completion of the first part (Phase I) of the study.

In the first part of the study, we will mainly examine the safety of KW-2478 and determine the

best dose of the drug. We may use the data for studying KW-2478 effects on your body and how

will your body treats the drug.

In the second part of the study, we will mainly study the how many of total participants are

actually getting better. We may use the data to study how long the drug takes to show benefits, if

any.

In the first part of study, 24 person will be registered and in the second part of the study, 77

additional (total: 101) persons will be registered.

The registration procedure will take about 22 months and your participation will be for 28

months after that.

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Study Sites:

This trial is taking place in different States of United States, United Kingdom and Philippines. This

particular form addresses United States population.

Here is the list of sites in the United States, where the study will be conducted. You may choose

your closest site to participate in the study.

1. Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,

Tucson, Arizona 85715

2. Pacific Shores Medical Group 1043 Elm Ave, Suite 104

Long Beach, California 90813

3. UCLA Medical Center Hematology / Oncology Division, 10945 Le Conte Ave #2333,

Los Angeles, California 90095

4. Collaborative Research Group 2320 S Seacrest Blvd, Suite 202

Boynton Beach, Florida 33435

5. Rush University Medical Center / Division of Hematology/Oncology Research 1725 W

Harrison Street, Suite 834

Chicago, Illinois 60612

6. Cancer Institute of New Jersey 195 Little Albany Street

New Brunswick, New Jersey 08903

7. The Jones Clinic 7710 Wolf River Circle

Germantown, Tennessee 38138

8. UT MD Anderson Cancer Center, 1515 Holcombe Boulevard,

Houston, Texas 77030

9. Gundersen Clinic Center for Cancer and Blood Disorders, 1900 South Ave, EB2-001,

La Crosse, Wisconsin 54601

STUDY PROCEDURES

This study is only open to patients who meet the previously described criteria. First it will be

performed a phase of selection: Three weeks prior of participating in clinical research, you will be

tested to determine if you qualify for the study. These tests are necessary to diagnose the multiple

myeloma and determine its degree of evolution.

Screening Tests

You will need to report three weeks prior to the clinical site if you decide to attend for the clinical

study. You will be required to have two screening visits.

NOTE: You will be given a plastic container to collect your urine. You will be required to

collect your urine for 24 hours the day before your scheduled screening visit 1.

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Screening visit 1:

This visit will take about two hours. The doctor will:

Collect the container with your urine (given to you at the time of reporting) for Serum free

light chain assays.

Perform a complete physical examination including weight, height, vital signs and

assessment of functional status.

Take your blood sample and ask for your urine sample.

Perform an electrocardiogram (ECG).

If you are a woman, the doctor will take your blood/urine sample for pregnancy test.

The following tests will be performed with your blood and urine samples:

1. Serum protein electrophoresis

2. Full blood cell count

3. Urea and electrolytes test

4. Calcium level

5. Beta-2 microglobulin level

6. Albumin level

If you would like to know more about above-mentioned tests, please ask your attending doctor.

If you qualify after screening visit 1 (you will be contacted), you have to report for screening

visit 2 within a week.

Screening visit 2

This visit will take about three hours. The doctor will take two samples of your bone marrow for

biopsy.

Sample Collection 1:

You will be given a small injection to numb the area near your hip bone. The doctor then gently

passes a needle through your skin into the bone. A sample of your liquid marrow will be drawn

into a syringe. The procedure will take about 15–20 minutes. You may feel little uncomfortable

for few minutes. If you feel pain or discomfort, please let the doctor knows. He may give you a

sedative.

Sample Collection 2:

The doctor will take a small core of marrow from the bone. This procedure will take about 30

minutes. A special type of needle will be used to collect the sample through the skin and bone

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into the bone marrow. The doctor will push the biopsy needle in and gently turn it back and forth

and then remove it. You may feel pain at the injection site for few days. If you prefer, the doctor

can give you painkillers.

X-Ray:

After the samples are taken, you will be moved to the X-Ray room. The specialist will take X-

rays of your whole body to check for any possible damage to the bones from the myeloma cells.

This will take about an hour.

Once you passed all the screening tests, you will be notified about the starting date and time of

the research study.

Scheduled Visits:

The study duration will take about 28 months.

Visits for Phase I study:

This part of the study will take about 16 months. There will be 8 cycles of treatment, each

consisting of 2 months. You will go to hospital 5 times during each cycle of treatment. These visits

will be scheduled on days 1, 4, 8, 11 and 21. Each visit will take up to 3 hours.

1. Visits on days 1, 4, 8 and 11: You will be given Bortezomib as an injection into a vein

which takes just a few seconds. Then you will be given KW-2478 through a drip which

takes about an hour.

2. Between day 11 and 21 you will not receive any drug.

3. Visit on day 21: The doctor will examine you and collect your blood and urine samples

for laboratory testing.

4. There will be one-month wait period until the next cycle begins.

These steps will be repeated eight times for the scheduled cycles.

One month after the last cycle is completed; the doctor will examine you if you are benefitting

from the treatment. If doctor decides to continue you for the next part of the study, he will notify

you.

If you hear back from your treating doctor and you would want to discontinue, please notify him.

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Visits for Phase II study:

This part of the study will take about a year. There will be 6 cycles of treatment, each consisting

of 2 months. You will follow the identical schedule for visits as you did in phase I.

You will go to hospital 5 times during each cycle of treatment. These visits will be scheduled on

days 1, 4, 8, 11 and 21. Each visit will take up to 3 hours.

1. Visits on days 1, 4, 8 and 11: You will be given Bortezomib as an injection into a vein

which takes just a few seconds. Then you will be given KW-2478 through a drip which

takes about an hour.

2. Between day 11 and 21 you will not receive any drug.

3. Visit on day 21: The doctor will examine you and collect your blood and urine samples

for laboratory testing.

4. There will be one month wait period until the next cycle begins.

These steps will be repeated six times for the scheduled cycles.

RISKS OF PARTICIPATION

While participating in the study, the risk of side effects arising from any of the drugs used may

appear. If they do, they may be mild, moderate or severe. In this study, you may also have different

side effects depending on the treatment that will be assigned to you.

If you suffer any side effects that the medical team had not noticed, please immediately talk to the

study staff. It is necessary to communicate as soon as possible in order to examine you and give

you the treatment, which is accurate.

Other drugs and supplements can affect the activity of the study medication (KW-2478 in

Combination with Bortezomib). Please remember to inform your study doctor of all medications

and supplements you take during the course of it.

Regarding the experimental study drugs (KW-2478 in Combination with Bortezomib), there can

be a possibility of experiencing some rare or unknown side effect. It is very unlikely to happen;

we are trying to make sure that you are aware of those situations.

We have mentioned the expected side effects of both drugs given to you in the research study on

next page (page 8).

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Common side effects of Bortezomib

The most common side effects associated with Bortezomib are:

Headache

Taste changes

Trouble sleeping

Weakness

Peripheral neuropathy: The damage to the nerves in the extremities (arms / hands and legs

/ feet), which results in altered sensitivity and / or pain. The most characteristic symptoms

are numbness, tingling, increased sensitivity, noting the soles of the feet cold, but

sometimes it is a burning sensation.

Decreased blood cells: It can lead to the development of anemia.

Hypotension: decrease in blood pressure

Gastrointestinal problems: constipation, mild stomach pain, nausea or vomiting, stomach

upset, diarrhea or feeding intolerance

Fatigue, dizziness

Rashes

Other less common side effects: As with other drugs, there are side effects that can be

potentially serious but those are rare. It is, therefore, advisable to report the development

of any unexpected symptoms arising during treatment as soon as possible.

This drug will harm the fetus if taken during pregnancy.

Side effects of KW-2478

KW-2478 is a new drug so there may be side effects that we do not know about yet. From an earlier

study, researchers know that side effects can include

Headache

Runny nose

Raised blood pressure

Diarrhea

Constipation

Feeling or being sick

Tiredness (fatigue)

Back pain or other pain

It may also affect your eyes, causing problems such as blurred vision. Therefore, it is important to

let the trial doctors know if you notice any changes to your vision.

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UNFORSEEN RISKS

You should consider that might arise unforeseen risks or unknown effects during the study.

However, if you manifest a severe adverse effect during the clinical trial, the investigator will end

your participation in the process and provide the necessary treatment to your condition.

BENEFITS OF PARTICIPATION

It is proved that Bortezomib helps people with relapsed multiple myeloma live longer. However,

the advantages of the combination of the drugs (KW-2478 and Bortezomib) are unsure; therefore,

you may not get any benefits from this study.

Nevertheless, if you do not benefit with this treatment, the results of this study, in the case they

were not positive, will help researchers learn more about the disease and the new treatments, which

will undoubtedly help others patients in the future.

AWARENESS ABOUT NEW FINDINGS

We will make you aware, if we have new information that might change your mind about

participating in this research study. If you want to end your participation, you should feel

comfortable to talk to the study doctor. We will make sure you can withdraw from the study in

safest way possible. The study doctor will discuss with you the different options for withdrawing

from the study.

ALTERNATIVE TREATMENTS

There are other treatments available to treat the relapsed and/or refractory multiple myeloma.

Examples of these treatments are the use of drugs like Bortezomib by itself, thalidomide and

lenalidomide. The use of these drugs have dramatically improved the life expectancy for patients

with relapsed myeloma. The investigator or his staff will talk about these other drugs with you.

Remember that only you can make the decision to participate or not in the study and receive,

instead, a routine treatment.

COMPENSATION

We will not pay you for your participation in the research. We may pay for your travel expenses,

if you are commuting to get to the research study site for scheduled visits and tests. The maximum

limit of travel reimbursement is $250/month. If you spend more than $250/month, you will be

responsible for additional expenses.

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ADDITIONAL COST TO YOU (PARTICIPANT)

There will not be any additional cost to you for participation in the study. The sponsor will cover

all the cost for the study drug, screening procedures, study procedures and necessary laboratory

testing related to the study.

If you schedule additional Doctor’s visit or laboratory tests outside the study, that will be billed to

your insurance. We are not liable to cover any costs outside the research study.

If you do not have insurance and would like to know more about additional costs and coverage,

you can call our help-line number (201) 350-3501.

IN CASE OF INJURY DURING RESEARCH STUDY

If you experience an injury related to the investigation, you will be provided emergency medical

treatment at no cost to you. This applies from the moment that you agree to participate in the study

by signing this document, to the moment you finish your participation in the project or you

withdraw your consent. Signing this informed consent form do not waive your legal rights, nor

affect the legal and professional liability of researchers, sponsor or participating institutions.

CONFIDENTIALITY OF RECORDS

Your records obtained while you participate in this study and related health records, remain

confidential as far as possible. However, they must be available to the members of the Ethic

Committee and Regulatory Authorities, if required by law.

By signing the consent form, you grant this access for the current study and any further research

that can be performed using this information. Nevertheless, the investigator of the study will take

steps to protect your personal information, and will not include your name in any form, publication

or disclosure. If you leave the study, we will not get more personal information about you, but we

will need to continue using the information already collected.

The company will contact your Primary Care Physician if you are injured or experiencing severe

problems/ illness during the research study. All the information from your research participation

will be disclosed to your primary care physician.

The company will post a description of this clinical trial on http://www.ClinicalTrials.gov. That

posting is mandatory because of the requirements in U.S. Law. This Web site will not include

information that can identify you. The website will only have the description of study and study

results. The website is open for public to assess information about clinical studies.

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WHOM TO CONTACT

For Questions regarding Research study Phone No. (201) 350-3500

For Questions regarding Cost for Study Phone No. (201) 350-3501

Additional Contacts:

Study Director: Michael Kurman, MD Phone No. (201) 510-9766

Study Chair: Loan Hoang- Sayag, MD Phone No. (201) 217-4631

Study Chair: Noel Pingoy, MD Phone No. (201) 268-4031

IF IT IS AN EMERGENCY AND YOU ARE NOT AT CLINICAL STUDY SITE, PLEASE

DIAL 911.

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SIGNATURES:

Mark with an X if you meet what is mentioned.

I have been informed about the study and had my first conversation with the study doctor or

research staff on such information on (Date) _____________ when (if necessary) ________. (The

time is necessary only if the information and consent were delivered the same day.)

I have read and understand the information in this document called informed consent.

I have had the opportunity to ask questions and all my questions were answered to my

satisfaction.

I voluntarily consent to participate in this study. I not waive any of my legal rights by signing

this consent.

I understand, I will receive a signed and dated copy of this document, which has a total of 13

pages.

______________________________________________ _________________

Participant name Participant Signature

__________________ _______________

Date signature Time (if required)

______________________________________________ ________________

Name of legally authorized representative Relationship

__________________ _______________ __________________

Signature of legally Date signature Time (if needed)

Authorized representative

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Impartial witnesses

_____________________________________ ______________________________________

Impartial Witness Name 1 Impartial Witness Address 1

________________________________________

Relationship

________________________ ___________________ _________

Impartial Witness Signature 1 Date Time

_____________________________________ _____________________________________

Impartial Witness Name 2 Impartial Witness Address 2

________________________________________

Relationship

________________________ ___________________ _________

Impartial Witness Signature 2 Date Time

Person Obtaining Consent

_____________________________________

Name of the person who conducted the consent process

________________ _______________ __________________

Signature Date signature Time (if required)

The time is necessary only if the information was provided on the same day that the consent or consent and

any specific activity of the study would be conducted on the same day.

The investigator or a suitably qualified and competent person designated by the investigator to lead the

process of informed consent must sign and date the form at the same time as the subject.

Impartial Witness: A person, who is independent of the trial, who cannot be unfairly influenced by people

involved with the trial, who attends the informed consent process if the subject or the subject’s legally

acceptable representative cannot read, and who reads the informed consent form and any other written

information supplied to the subject.

Guide E6 Good Clinical Practice for Industry: Consolidated Guidance.

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REFERENCES

1. A Guide to Informed Consent - Information Sheet. (2014, 6 25). Retrieved from U.S Food

and Drugs Administration:

http://www.fda.gov/RegulatoryInformation/Guidances/ucm126431.htm#general

2. A Study of KW-2478 in Combination with Bortezomib in Subjects with Relapsed and/or

Refractory Multiple Myeloma. (2014, 12 1). Retrieved from ClinicalTrials.gov:

https://clinicaltrials.gov/ct2/show/NCT01063907?term=A+Study+of+KW-

2478+in+Combination+with+Bortezomib+in+Subjects+with+++Relapsed+and%2F+or+

Refractory+Multiple+Myeloma&rank=1

3. Benefits of VELCADE® (bortezomib). (2014, 6). Retrieved from Velcade:

http://www.velcade.com/Treatment-with-velcade/Benefits-of-velcade

4. ECOG Performance Status. (2015, 01). Retrieved from ECOG- ACRIN cancer Research

Group: http://ecog-acrin.org/resources/ecog-performance-status

5. Guidance for Industry. E6 Good Clinical Practice: Consolidated Guidance. (1996, 04).

Retrieved from U.S Food and Drug Administration :

http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf

6. How Myeloma is diagnosed. (2013, 2 1). Retrieved from We are Macmillan cancer

support:

http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Myeloma/Symptomsdiagn

osis/Diagnosis.aspx

7. Informed Consent to particiapate in research. (2015, 04). Retrieved from NorthEastern

University online: https://nuonline.neu.edu/bbcswebdav/pid-8226641-dt-content-rid-

11357505_1/courses/BTC6210.80469.201535/Example%20Student%20ICF%20A%20G

rade.pdf

8. John P. Cunha, D. F. (n.d.). Velcade Side Effects Center. Retrieved from RXList:

http://www.rxlist.com/velcade-side-effects-drug-center.htm

9. Kyowa Hakko Kirin Pharma, I. (2014, 12 1). A Study of KW-2478 in Combination With

Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma. Retrieved

from ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT01063907

10. PATIENT INFORMATION, INFORMED CONSENT, AND AUTHORIZATION TO

ACCESS MEDICAL RECORDS. (2013, 03 28). Retrieved from thewritecenter.org:

http://www.thewrightcenter.org/wp-content/uploads/2013/05/Agenda-Section-7.1-

C16014-ICF.pdf

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11. Screening Consent. (2014, 09 29). Retrieved from web.emmes.com:

https://web.emmes.com/study/bmt2/protocol/0702_protocol/0702%20Consent%20Forms

%20v7.pdf

12. Timothy Moynihan, C. N. (2014, 09 11). Multiple Myeloma. Retrieved from

MayoClinic.org: http://www.mayoclinic.org/diseases-conditions/multiple-

myeloma/basics/definition/con-20026607

13. Velcade. (2015, April 01). Retrieved from Drugs.com:

http://www.drugs.com/cdi/velcade.html