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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
