Conditions: Degradation of Top2b and Top2a in Human by Dexrazoxane Time Course and Degradation of Top2b in Human by Dexrazoxane Effects of Dexrazoxane on Healthy Human
Keywords: Dexrazoxane Topoisomerase 2b Human Doxorubicin cardio-toxicity Cardio-oncology Onco-cardiology Prevention of cardio-toxicity by doxorubicin Early administration of dexrazoxane
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 25
Healthy volunteers: yes

Brief summary:
The purpose of this research study is to determine whether early administration of Dexrazoxane prevents Doxorubicin induced cardiotoxicity.

Detailed description:
This is a study on volunteers to determine effective dose of dexrazoxane in degrading Topoisomerase 2 b in human blood samples. Each participant will receive one dose of dexrazoxane. Blood samples will be collected to determine the time course and degradation of Topoisomerase 2b and Topoisomerase 2a

Arms:
arm 1: one dose of 100mg/m2 dexrazoxane arm 2: one dose of 200mg/m2 dexrazoxane arm 3: one dose of 300mg/m2 dexrazoxane arm 4: one dose of 400mg/m2 dexrazoxane arm 5: one dose of 500 mg/m2

Interventions: intervention 1: Dexrazoxane
Intervention descriptions: intervention 1: One dose of dexrazoxane

Protocol document:
ICF_001.pdf: 
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CONSENT FORM AND INFORMATION ABOUT 
 
Prevention of Heart Failure Induced by Doxorubicin with Early 
Administration of Dexrazoxane (PHOENIX 1) 
 
to be conducted at 
THE UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES 
 
Principal Investigator: 
Hui-Ming Chang, M.D., M.P.H. 
4301 West Markham, Slot #724 
Little Rock, AR  72205 
Phone: (501) 686-8274 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant Name  
 
 
 
 
Medical Record Number 
 
Key Information for Prevention of Heart Failure Induced by 
Doxorubicin with Early Administration of Dexrazoxane (PHOENIX 1) 
 
This first part gives you key information to help you decide if you want to join the study. 
We will explain things in more detail later in this form.  
We are asking if you want to volunteer for a research study about the use of dexrazoxane 
in cancer patients. By doing this study, we hope to find a lower  effective dose of 
dexrazoxane to prevent heart failure induced by doxorubicin. 
Please ask the research team if you have any questions about anything in this form. If you 
have questions later, contact the researcher in charge of the study. The contact information 
is at the top of this page.  
What will happen if I join the study?   
If you are eligible for this research study, your part in this research may last up to one 
week and include five visits. 
During the study, you will receive a single IV infusion of dexrazoxane and have blood 
drawn at multiple time points. We will explain this process later in this form. 
The purpose of the study is to learn whether a dose lower than the FDA approved dose 
would be effective.  


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Do I have to join this study?  
No. It is okay to say no. You will not lose any services, benefits, or rights you would 
normally have if you decide not to join. If you decide to take part in the study, it should 
be because you really want to volunteer.  
What do I need to know to decide if I should join this study? 
People decide to join studies for many reasons. Here are some of the main things you 
should think about before choosing to join this study.   
Main reasons to join the study 
 There is no direct benefit to you but the knowledge gained may help in the future 
treatment of people with cancer.  
Main reasons not to join the study 
 You may experience discomfort or pain during the IV infusion or blood draw.  
 There is a potential for loss of confidentiality. Someone may find out you were 
in this study and learn something about you that you did not want them to know. 
These are just some of the reasons to help you decide if you want to join the study. We 
will explain more about the risks, benefits, and other options to joining the study later in 
this form.  
 
 
 
 
 
 
Tell the study team if you decide that you do not want to be in the study. Remember, it is 
okay to say no. You can still get your medical care from UAMS if you are not in the study.  


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University of Arkansas for Medical Sciences Informed Consent Form 
Why am I being asked to be in this research study? 
 We want to learn more about the use of dexrazoxane in cancer patients. 
 By doing this study, we hope to find the dose of dexrazoxane that will be effective 
to prevent heart failure induced by doxorubicin. 
 We are asking people like you, who are healthy female volunteers to help us.  
 We will consent up to 50 people, adults, 18-65 years of age, in order to enroll 25 
to the study. 
What if I don’t understand something? 
 This form may have words you do not understand. If you would like, research staff 
will read it with you.  
 You are free to ask questions at any time – before, during, or after you are in the 
study. 
 Please ask as many questions as you would like before you decide if you want to 
be in this study.  If you decide to take part in the study, it should be because you 
really want to volunteer. 
 
 
 
- We are asking you to be in a research study. You do not have to join the study. 
- You can still get your medical care from UAMS even if you are not in the study. 
- Take as much time as you need to read this form and decide what is right for you. 


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What will happen if I say yes, I want to be in this study?  
 
You may be screened for COVID each time you come to the Winthrop P Rockefeller 
Cancer Institute, depending on the UAMS standards.  
There will be five visits in this study. We will draw blood at each visit.  
Visit 3, 4, and 5 are visits to have one blood drawn of 2 teaspoons. 
Visit 1 
During the first visit, we will see if you qualify to be in the study.  We will: 
 Ask you some questions about your heath and medicines you may be taking. 
 Obtain a blood sample to check your liver and kidney functions and make sure you 
are not pregnant or have anemia. A urine pregnancy test can be used in place of 
the blood sample to test if you are pregnant.  
 Check your vital signs. We will record your height, weight, heartbeat, respirations, 
blood pressure, and temperature. We will ask you to rate your pain on a scale from 
1-10. 
If you qualify, we will do these things: 
This study has five groups. Each group will receive a designated dose of dexrazoxane. 
You will be assigned to the current study group. 
A time will be scheduled for you to return to the study site to begin your participation.  
 
Visit 2 
For your second visit, you will go to the Winthrop P Rockefeller Cancer Institute. Prior to 
your 12-hour infusion, you will need to take a urine pregnancy test. You will receive an 
intravenous (IV) catheter (a small plastic tube inserted through a needle into a vein on 
your arm). About 4 teaspoons of blood will be drawn from this IV line for baseline blood 
tests.  You will receive dexrazoxane through IV infusion for 15 minutes (+/- 5 minutes).  
 
Two teaspoons of blood will be drawn hourly from the IV catheter for the next 12 hours. 
Meals vouchers will be provided to you during this 12 hour infusion visit at Visit 2.  
 
We will check your vital signs before and after the infusion, six hours after the infusion, 
and 12 hours after infusion when you are discharged. We will record your heartbeat, 
respirations, blood pressure, and temperature. We will ask you to rate your pain on a scale 
from 1-10.  
 


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On visits 2, 3 and 4, we will be testing your blood for two enzymes. These enzymes 
indicate how well dexrazoxane is working in your body. 
 
Visit 3 
You will go to the Winthrop P Rockefeller Cancer Institute. You will have blood drawn 
24 hours after dexrazoxane infusion. 
 
Visit 4 
You will go to the Winthrop P Rockefeller Cancer Institute. You will have blood drawn 
48 hours after dexrazoxane infusion. 
 
Visit 5 
You will go to the Winthrop P Rockefeller Cancer Institute. To make sure you do not have 
a very rare side effect, you will have blood drawn for routine blood count one week after 
the infusion. If your blood test shows a need for follow up, you will have an additional 
test one week later. The cost of the additional visit will be paid by the study, however, no 
additional payment will be provided.   
We will take a total of about 34-38 teaspoons of blood for the whole study. You will be 
monitored for any symptoms you may experience.  
 
You will need to refrain from drinking alcohol until you have completed your 48th hour 
blood draw after infusion. 
 
The IV infusion and all blood samples are required to participate in this study. The 
collections of blood are for research only.  
You will be given a parking voucher for each visit. 
How long will I be in this study?  
You will be in the study for about 1 week. There will be five visits, including one visit 
that will last for about 12 hours. During this extended visit, you will have blood drawn 
(through your IV) once an hour for 12 hours. During this visit, meals will be provided to 
you. 
You will return to have your blood drawn 24 hours after your infusion and then again at 
48 hours after your infusion. 
Finally, one week after your infusion, you will return to the study site for a blood draw.  
You will be given a parking voucher for each visit. 


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What if I say no, I do not want to be in this study? 
 Nothing bad will happen because of what you decide.  
 You can still get medical care at UAMS.  
What happens if I say yes but change my mind later? 
 You can stop being in the study at any time.  
 Nothing bad will happen because you change your mind and leave the study.  
 You can still get medical care at UAMS. 
 If you decide to stop being in the study, inform a member of the study team.   
Will it cost me anything to be in the study? 
The study will not cost you anything. You and/or your health insurance will be required 
to pay for those services, supplies, procedures and care that you continue to require for 
your routine medical care during this study (meaning the procedures and services you 
would have had even if you were not in the study). You will be responsible for any co-
payments and/or deductibles as required by your insurance for such routine medical care.  
Will I be paid for being in the study? 
Yes. You may be paid a total of $400. This is to reimburse you for your time and 
inconvenience. You will be issued a Greenphire, Inc. ClinCard, which is a debit card that 
your stipends are loaded onto and can be used at your discretion. When a visit is 
completed, funds will be approved and loaded onto your card. Once approved to be 
released to your card, the funds will be available for use. 
If you change your mind and decide not to complete the study, you will only be paid for 
the parts you complete. You will be paid $50 for the screening portion of this study. You 
will be paid $80 for receiving the infusion. You will be paid $120 ($10 per blood draw) 
to complete the first 12 hours of blood draws. You will receive an additional $50 for each 
return visit to the study site for blood draws (at 24 hours, 48 hours and one week after the 
infusion). If your lab values require you to return for the additional, conditional visit two 
weeks after the infusion, the cost of your visit will be paid by the study, however, you will 
not receive any additional compensation. A parking voucher will be provided for each 
visit. Meals will also be provided to you during the 12 hour infusion visit at Visit 2.   


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In accordance with the United States IRS guidelines, payments paid to an individual that 
are equal to or greater than $600.00 per calendar year (January-December) are reportable 
to the IRS.  If your payments are equal to or greater than $600.00 in a calendar year, you 
will receive a 1099-MISC form to file with your taxes. The 1099-MISC will be sent in 
January of the following year as required by the IRS. If your payments were not greater 
than $600 in the calendar year, you will not receive a 1099-MISC form.  No taxes will be 
withheld from payments made to you. You are responsible for reporting payments to you 
on your state and federal tax returns, as applicable, and paying any taxes that may be due. 
If you are a recipient of Social Security Income (SSI), Social Security Disability Income 
(SSDI) recipient, or other income based assistance programs, the additional income from 
this study will increase your yearly income and possibly make you ineligible for these 
benefits. Please ask your study coordinator for details.  Please contact your Social Security 
Office or your financial advisor if you have any questions 
Will being in this study help me in any way? 
We do not think that being in this study will help you personally. However, it may help 
people with being treated for cancer in the future.  
What are the risks of being in this study? 
There is a risk that someone could find out that you were in the study and learn something 
about you that you do not want others to know. We will do our best to protect your privacy, 
as explained in more detail later in this form.  
Blood testing risks: Taking blood from you may cause some discomfort from the needle 
stick, bruising, or very rarely, infection. 
Possible risks, discomforts, and/or side effects of dexrazoxane include:  
 Pain on injection: This is the most likely side effect.   
To reduce the likelihood of this side effect, we will administer dexrazoxane 
through infusion, not injection. If needed, we will check your catheter and slow 
down the infusion rate to minimize this side effect. 
 The superficial skin and deeper tissue under the skin might suffer damage (tissue 
death):  
Notify study staff if you experience this side effect. (very low likelihood, not 
serious) 
 Myelosuppresion (reduced blood counts) 
We will ask you to have blood drawn for blood counts one week after you received 
dexrazoxane infusion. (low likelihood, serious) In the very rare situation that you 


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have reduced blood counts, we will help you get further observation and medical 
care at UAMS or your local provider.  This treatment will be billed to you or your 
insurance company.  
 Severe allergic reaction, such as anaphylaxis. Anaphylaxis is a serious, potentially 
life-threatening, whole-body allergic reaction.: (very low likelihood, serious)  
If you develop an allergic reaction to dexrazoxane, the infusion will be stopped. 
Other common possible side effects that may need medical attention: 
 Bluish color  
 changes in skin color  
 chest pain  
 chills 
 cold hands and feet  
 cough  
 difficult or labored breathing  
 fever  
 hoarseness  
 lower back or side pain  
 pain, redness, or swelling in the arm or leg  
 painful or difficult urination  
 pale skin  
 sneezing  
 sore throat  
 swelling of the hands, ankles, feet, or lower legs  
 tenderness  
 tightness in the chest  
 troubled breathing  
 unusual bleeding or bruising  
 unusual tiredness or weakness 
Due to the risk of myelosuppression (reduced blood counts), you should not take aspirin, 
NSAIDs, and over-the counter supplements for at least 1-2 weeks after infusion of 
dexrazoxane.  
Report fever, any bleeding from gums or nose, blood in stool or urine. If you experience 
any of these, you may need an earlier visit to evaluate for myelosuppression.  
 
 
 


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What if I get sick or hurt while I am in this study? 
If you get hurt or sick when you are here for the study, we will help you get the care you 
need. This may include first aid, emergency care, and any follow-up care you need. 
 If you are not here and get hurt or sick, and you think it is because of the study, do 
these things: 
 call your doctor – or if an emergency, call 911  
 give your doctor or ER staff  
o the name of this study – Prevention of Heart Failure Induced by 
Doxorubicin with Early Administration of Dexrazoxane (PHOENIX 1) 
o the name of the head researcher for this study – Hui-Ming Chang, MD 
o a copy of this form if you have it 
 after business hours, call (501) 686-7575, or (501) 526-0847   
 This treatment will be billed to you or your insurance company. No other form of 
payment is available. 
 
Reminder: You do not give up any of your legal rights by agreeing to be in this study or 
by signing this form. 
 
What are the alternatives to being in this study?  
You may choose to not participate in this study. 
 
Can I be taken out of the study even if I want to continue?  
Yes, the study doctor can take you out of the study if: 
 You do not follow study instructions. 
 It is not in your best interest to continue. 
 The study is stopped for any reason. 
What information will be collected about me in the study?  
During the study, we will need to learn private things about you, including: 
 General contact and background information about you, such as age, race, and other 
demographic information. 


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 Results of physical exams, lab tests, and your response to study treatment and side 
effects, as well as your history of previous illnesses and conditions that you have 
now.  
Who will see this information? How will you keep it private?  
 The study team will know your name and have access to your information.  
 We will do our best to make sure no one outside the study knows you are part of 
the study.  
 We will take your name off the study information that we collect from you during 
the study.  
 We will give your information a code, so that no one can identify you. 
 If we share the results of the study in medical journals or other publications, we 
will not include your name or anything else that could identify you.  
 There are people who make sure the study is run the right way. These people may 
see information that identifies you. They are 
 OHRP (Office for Human Research Protections), a federal agency 
 UAMS Institutional Review Board  
 Other institutional oversight offices 
 State law requires that we tell the authorities if we learn about possible abuse or 
that you might hurt yourself or someone else. 
 
Where will my information be kept? For how long will it be kept?   
 Once we give your information a code, we will keep the key to this code in a 
locked file.  
 Only the study staff will be able to link it to you. 
 The information may be kept indefinitely on a password-protected file.  
 Your samples will be destroyed after the study is complete. 
 We will put information about you from the study in your medical record.  
 We will put a copy of this form in your medical record. 
 


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If I stop being in the study, what will happen to my information collected in the 
study?  
 If you wish to have your information taken out of the study, call Dr. Hui-Ming 
Chang at 501-686-8274. 
 
Will my information or samples from the study be used for anything else, including 
future research?  
No. Your information or samples will be used only for this study. It will not be used for 
future research, either with or without identifiers. 
Will you tell me the results of the study?  
No. However, we plan to publish the results in an academic journal. (What we publish 
will not include anything that can identify you though.)  
Will you tell me anything you learn that may affect my health?  
Yes. If we learn something about you that might be important for your health, we will tell 
you. 
What if new information comes up about the study? 
We will tell you if we learn anything that may change your mind about being in the study.  
 
Where can I find more information about this clinical trial?  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. law. This website will not include information that can identify you. At 
most, the website will include a summary of the results. You can search this website any 
time. 
What if I have questions? 
 Please call the head researcher of the study – Hui-Ming Chang at 501-686-8274– 
if you 
 have any questions about this study 
 feel you have been injured in any way by being in this study 
 You can also call the office at UAMS that supervises research if you cannot reach 
the study team, have questions about your rights as a research participant, or want 


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to speak to someone not directly involved with this study. To do so, call the 
UAMS Institutional Review Board at 501-686-5667 during normal work hours. 
 
By signing the document, I am saying: 
 I agree to be in the study. 
 I know that joining this study is voluntary. 
 Someone has talked with me about the information in this form and answered all 
of my questions.  
I know that: 
 I can stop being in any and all parts of the study at any time and nothing bad will 
happen to me.  
 I can still get medical care at UAMS no matter what I decide. 
 I can call the office that supervises research (UAMS Institutional Review Board) 
at 501-686-5667 if I have any questions about the study or about my rights. 
 I do not give up any of my legal rights by signing this form. 
I agree to be part of this study: 
 
____________________________  
 
____________________________ 
Your name (please print) 
 
 
 
Your signature 
___________________________ 
Date 
 
____________________________  
 
____________________________ 
Printed name of person obtaining consent 
 
Signature of person obtaining consent 
___________________________ 
Date 

Prot_000.pdf: 
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Study Title: 
Prevention of Heart Failure Induced by Doxorubicin with 
Early Administration of Dexrazoxane (PHOENIX 1) 
 
Principal Investigator: 
Hui-Ming Chang, M.D., M.P.H. 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot 611 
Little Rock, AR 72205 
Email: HChang@uams.edu 
 
Co-Investigator: 
Edward Yeh, M.D. 
University of Arkansas for Medical Sciences 
4301 W. Markham Street 
Little Rock, AR 72205 
Email: EYeh@uams.edu 
 
Safety Officer: 
Jawahar Mehta, MD., PhD. 
University of Arkansas for Medical Sciences 
4301 W. Markham Street 
Little Rock, AR 72205  
Email: MehtaJL@uams.edu 
 
Sponsor: 
University of Arkansas for Medical Sciences 
 
Study location: 
University of Arkansas for Medical Sciences 
Winthrop P. Rockefeller Cancer Institute 


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Background and Rationale 
Doxorubicin, an inhibitor of DNA topoisomerase 2a (Top2a), is routinely used in the 
treatment of breast cancer, sarcoma, and pediatric leukemia. Long-term cancer survivors 
who were treated with doxorubicin often suffer from dose-dependent cardiotoxicity. Of the 
two topoisomerase 2 isozymes, Top2a is highly expressed in cancer cells and is required 
for cell division. However, adult cardiomyocytes express only topoisomerase 2b (Top2b). 
Studies from our laboratory showed that Top2a mediates doxorubicin’s tumoricidal 
activity, whereas Top2b mediates doxorubicin’s cardiotoxic effect. At present, 
dexrazoxane is the only FDA-approved drug for cardio-protection. The cardio- protective 
effect of dexrazoxane is due to its ability to bind to the ATPase domain of Top2b  to inhibit 
Top2b’s catalytic cycle. Currently, dexrazoxane is administered concurrently with 
doxorubicin. The FDA recommended dose of Dexrazoxane is 10 times the dose of 
Doxorubicin. Because dexrazoxane also binds to Top2a, it has the potential to interfere 
with doxorubicin’s tumoricidal effect. Thus, dexrazoxane has limited clinical utility as 
specified by FDA’s approved indication. In preliminary studies, dexrazoxane induced an 
ubiquitin/proteasome-mediated degradation of Top2b, but not Top2a. By 
administering dexrazoxane eight hours before doxorubicin, Top2b will be degraded 
to avoid cardiotoxicity, whereas Top2a will remain intact to preserve tumoricidal 
efficacy. Because the half-life of dexrazoxane is two hours, 93.75% of dexrazoxane will 
be eliminated eight hours (four half-lives) after administration. Indeed, dexrazoxane pre- 
treatment eight hours before doxorubicin provided complete protection against 
doxorubicin-induced cardiotoxicity in our animal model. We propose to conduct an 
investigator-initiated clinical trial to test this hypothesis. We will use the results from this 
study to design a pilot clinical trial on breast cancer patients. 
 
Objectives 
Primary Objective: To determine the effective dose of Dexrazoxane pre-treatment in 
degrading topoisomerase 2 b (Top2b) in human peripheral blood. 
Secondary Objectives: To determine the time course of Top2b degradation in healthy 
human volunteers. To determine topoisomerase 2 a (Top2a) in human peripheral blood 
will not be degraded by Dexrazoxane 
 
Study Design and Procedures 
This is a Phase 1 trial to determine time course and dose of dexrazoxane pre-treatment 
for optimal degradation of Topoisomerase 2 b (Top2b) in human volunteers. The FDA 
recommended dose of Dexrazoxane is 10 times the dose of Doxorubicin. All the doses in 
this protocol are in the FDA approved range and have been prescribed for many years. 
There will be 5 cohorts for different doses: 100mg/m2, 200 mg/m2, 300 mg/m2, 400 
mg/m2, or 500 mg/m2. Our plan is to enroll up to 5 subjects per cohort. We will start with 
100 mg/m2 and analyze the Top2 protein level from up to five subjects. Doses will 
escalate to


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200 mg/m2, 300 mg/m2, 400 mg/m2, and 500 mg/m2. If 100 mg/m2 dexrazoxane is 
insufficient, we will increase the dose to find the optimal dose. 
A blood sample will be obtained at screening to rule out anemia, pregnancy and to 
determine liver and kidney functions. If the serum pregnancy test is not performed at the 
time of the initial screening blood draw and another attempt is required in order to perform 
this test, a urine pregnancy test can be used as a substitute. A urine pregnancy test will 
be done on the day of the 12-hour infusion visit, prior to infusion. 
Subjects will be administered a dose of dexrazoxane by IV infusion over 15 (+/-5) minutes. 
Blood will be drawn to purify peripheral blood leukocytes for Top2b and Top2a 
assessment using Western blot analysis. 20 mL of blood will be drawn before 
dexrazoxane infusion. 10 mL of blood will be drawn hourly (+/- 5 minutes) after the start 
of infusion for 12 hours. The final lab draw of the 12-hour infusion day may occur at 6:30 
pm based on facility and staff availability.  The final blood draws occur at 24 hours (+/- 2 
hours); and 48 hours (+/- 2 hours) from the start of infusion. A total of 17 blood samples 
will be drawn for each subject.   
 
Subjects will be screened for COVID at each visit per institutional standards.  Subjects who 
do not pass the screening will not be permitted to continue with the study. 
 
Vital signs will be recorded at the following time points: 1) screening, 2) pre-infusion, 3) end 
of infusion, 4) 6 hours post-infusion, 5) 12-hours post infusion/discharge. Vital signs to be 
captured include: heartrate; respirations; blood pressure; temperature; pain (rate pain on 
scale of 1-10). Height and Weight will also be recorded at screening. 
 
A parking voucher will be provided for each visit. During the first 12 hours after infusion, 
meals and a parking voucher will be provided. 
 
Each subject will have a safety CBC one week (+/- 2 days) after dexrazoxane infusion to 
rule out myelosuppression. If the one-week post-study blood counts are below normal 
range, subject will have additional CBC two weeks post-infusion. 
Treatment failure and subject removal criteria includes: subject noncompliance with blood 
draw, or, subject develops rare hypersensitivity reactions to dexrazoxane infusion. 
 
Study Population 
Subjects will be healthy females, ages 18 to 65 years. Up to 50 subjects will be screened 
in order to enroll up to 25 subjects. 
Results from this protocol will be used to support future research with breast cancer 
patients; therefore, only women will be enrolled in the study. The protocol was approved 
by NIH review panel and program officer to study only female participants. 


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We plan to enroll 5 subjects to each of the 5 cohorts for a total of up to 25 subjects. 
Participants will be recruited using the UAMS Translational Research Institute (TRI) 
Research Participant Registry, ARresearch.org. After the list of potential participants is 
obtained from TRI, we will contact the individuals via email, if indicated as their 
communication preference. The email we will use when communicating with potential 
participants is included in the IRB submission. 
 
Participants will also be recruited using the Facebook pages of UAMS, TRI, and the 
Winthrop P. Rockefeller Cancer Institute. Participants may also be recruited at 
Community or University events, or from within UAMS via word of mouth. 
Subjects will be asked to self-report on the inclusion/exclusion criteria. However, a 
baseline blood sample will be obtained to rule out anemia and pregnancy and to 
determine liver and kidney function. 
 
Inclusion Criteria 
• Female 
• Age 18-65 years 
Exclusion Criteria 
• Women who are pregnant or breastfeeding 
• Presenting with an acute illness (may re-screen again in two weeks if illness has 
subsided) 
• Anemia (Hb < 12 g/dL for females) 
• Calculated Creatinine Clearance less than 60 mL/min 
• Liver function tests outside of normal range 
• Unwilling to refrain from alcohol consumption for 48 hours 
 
Participants with medical information suggestive of a chronic medical condition may be 
excluded from the research at the enrolling physician’s discretion. 
Repeat screening blood tests may be done at the discretion of the enrolling physician 
and/or principal investigator. All screening tests will be paid for by the research grant. 
 
Risks and Benefits 
Some subjects may experience discomforts, or pain on intravenous injection of 
dexrazoxane. We will minimize this risk by administering dexrazoxane as an IV infusion 


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over 15 (+/-5) minutes. If a participant reports pain during the infusion, the catheter will 
be checked to ensure it is properly inserted. If no problems are noted with the catheter, 
the  rate of the infusion will be slowed. There is a very low probability that a subject may 
develop subcutaneous and cutaneous necrosis. Subjects will be informed and instructed 
to report to study team if she develops this side effect. PI and study team members will 
arrange for medical care and expect full recovery on this. 
To reduce the risk of bruising and pain from multiple injections, the twelve hourly blood 
draws will be drawn from the IV catheter. If the initial IV line stops working for any reason, 
a new line will have to be placed. 
There is a very low probability that a subject may develop myelosuppression. Each 
subject will have screening CBC one week after dexrazoxane infusion to rule out 
myelosuppression. The study team will arrange for medical care and expect recovery if a 
subject develops myelosuppression. If the one-week post-study blood counts are not 
within normal range, subject will have additional CBC at 2 weeks post-infusion. 
The risk of allergic reaction is very low. In a rare situation, if the participant develops 
allergic reaction to dexrazoxane, the infusion will be stopped. 
Other adverse events may include: 
• Bluish color 
• changes in skin color 
• chest pain or tightness in the chest 
• chills 
• cold hands and feet 
• cough, sneezing, sore throat 
• difficult or labored breathing 
• fever 
• hoarseness 
• lower back or side pain 
• pain, redness, or swelling in the arm or leg 
• painful or difficult urination 
• swelling of the hands, ankles, feet, or lower legs 
• tenderness 
• unusual bleeding or bruising 
• unusual tiredness or weakness) 
All unanticipated problems or deviations should be reported immediately to principal 
investigator/sponsor. The immediate reports should be followed promptly by details 
written reports to investigator/sponsor. All reports will identify subjects by unique code 
numbers assigned rather than other identifiers. Unanticipated problems will be reported 
to IRB within 5 days of becoming aware of an event. 
A risk to study participants is the potential for loss of confidentiality of study data. 


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Measures to protect the confidentiality of study data will be implemented as described in 
the Data and Safety Monitoring Plan section below. 
There will be no direct benefits to the study participants; however, knowledge gained from 
the study could potentially benefit patients in the future. 
 
 
Subject Compensation 
Subjects completing all study visits will receive $400 compensation for their time. Subjects 
will be issued a Greenphire, Inc. ClinCard, which is a debit card that the stipends are 
loaded onto and can be used at their discretion. When a visit is completed, funds will be 
approved and loaded onto the card. Once approved to be released to the cards, the funds 
will be available for use. 
 
Subjects who partially complete the study will receive prorated compensation as 
described below.   
 
Screening - $50 
 Infusion – $80 
12-hr blood draws – $10 per blood draw (maximum of $120) 
24-hr blood draw – $50 
48-hr blood draw – $50 
1-week post infusion lab draw - $50 
 
A parking voucher will be provided for each visit.  Meals vouchers will also be provided to 
the subjects during the 12 hour infusion visit at visit 2. 
 
DATA AND SAFETY MONITORING PLAN 
Overall framework for safety monitoring and what information will be monitored. 
 
Plan for data management: A password-protected database will be used to manage all 
study data. To ensure confidentiality only subject ID numbers will be entered into the 
database. 
 
Paper records will be stored in the the PHOENIX 1 Clinical Trial office.  The records are 
stored in a double locked file cabinet, in the locked office. Only study staff will have 
access. Consent and HIPAA will have direct identifiers. Other paper source documents 
will be coded and the key to the code will be stored separately. Data from the de-identified 
source documents will also be stored on a password locked Microsoft Excel Spreadsheet 
located in a secure Box folder.  Only study staff will have access to this document.  
Records may be retained indefinitely, and at minimum, will be retained in accordance with 
institutional policy and applicable regulatory requirements. A UAMS approved vendor will 
be used to destroy documents. The key to the code will be destroyed at this time and 
thereby creating a de-identifiable data with the exception of the consent. 
 


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Participants will not be individually identified in any publication. Participants’ right to 
privacy will be protected. 
Plan for safety monitoring: The data and safety monitoring plan (DSMP) for this trial 
focuses on close monitoring by the PIs and the safety officer. QA monitoring will also be 
performed by independent Winthrop P. Rockefeller Cancer Institute staff. 
 
Frequency of monitoring: Monitoring will include enrollment, attrition, efficacy end- 
points, and adverse events. In addition to monitoring by the PIs, study coordinator, and 
safety officer monitoring, the University of Arkansas for Medical Sciences IRB monitors 
all aspects of the project on an annual basis. The frequency of the structured data  review 
for this study can be summarized below. 
 
Data type Frequency of review 
Subject accrual (adherence to protocol regarding demographics, inclusion/exclusion): At 
the end of each recruitment 
Adverse event rates (injuries): semi-annually 
Compliance to treatment: semi-annually 
Out of range laboratory data: semi-annually 
Stopping rules report regarding statistical power implications of dropouts and missing 
data: semi- annually 
IRB review: annually 
 
Process for Managing and Reporting Adverse Events, Serious Adverse Events and 
Unanticipated Problems: 
Unanticipated events will be reported to UAMS IRB, and both serious and non-serious 
adverse events will be reported to the Safety Officer. Adverse  events will be categorized 
and classified according to Common Terminology Criteria for Adverse Events Scale 
(CTCAE v5.0). Safety reports will be sent to the safety officer. Serious adverse events 
will be reported to the NIH Office of Biotechnology Activities, the  funding IC, and the FDA, 
in addition to UAMS IRB. The PI will be responsible for assembling the data and producing 
these reports, as well as assuring that  all parties obtain copies of these reports. 
 
Qualifications and responsibilities of the Safety Officer: 
The safety officer for this trial will be Jawahar (Jay) Mehta, MD., PhD. Dr. Mehta is a 
Distinguished Professor of Medicine, and Physiology and Biophysics, and the 
Stebbins Chair in Cardiology at UAMS. Dr. Mehta serves or has served on the editorial 
board of numerous journals including the American Journal of Cardiology; Circulation; 
Hypertension; Journal of the American College of Cardiology. Dr. Mehta has been funded 
numerous times by the Department of Veterans Affairs, the American Heart Association, 
and the National Institutes of Health. In 2017, he was ranked among the top 27 
cardiologists in the nation. As Safety Officer, Dr. Mehta will review eligibility criteria with 
Dr. Chang. He will review all reports sent by the study coordinator to determine whether 
there is any corrective action, trigger of an ad hoc review, or stopping rule violation that 
should be communicated to the UAMS IRB. In addition, the safety officer 


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may comment on whether the study PI needs to report any specific out- of-range 
laboratory data. 
 
 
Specimen Handling and Storage 
Specimens will be collected in the Winthrop P. Rockefeller Cancer Institute. Study staff 
will obtain the blood samples at the prescribed time intervals. Staff will label the tubes  with 
only the unique code and take them directly to the lab. Identifiers will not be included on 
the tubes. CTO staff will call  Dr. Jinn-Yuan Hsu or the assigned study staff to pick up the 
specimens. The specimens will be retrieved immediately and taken to the laboratory of 
the principal investigator to be processed and analyzed. Only the PI and study team will 
have access to the samples. After all the samples have been tested, the samples will be 
discarded. 
 
Data Analysis 
The goal of this protocol is to find the effective dose of dexrazoxane in degrading Top2b 
for the subsequent randomized clinical trial. We will select a dose of dexrazoxane, which 
reduces Top2b to less than 5% of baseline level in 8 hours in 5 volunteers. FDA 
recommended dose of dexrazoxane is 10 times the dose of doxorubicin. In the attached 
FDA approval documentation of dexrazoxane, 500mg/m2 is cited as a recommended 
dose. We will study dose levels 500mg/m2 or below. Healthy volunteers will be 
administered a dose of dexrazoxane. Blood will be drawn to purify peripheral blood 
leukocytes for Top2b and Top2a assessment using Western blot analysis. The following 
time points will be assessed: Pre-infusion,1,2,3,4,5,6,7,8,9,10,11,12,24, and 48 hours 
after start of dexrazoxane infusion. Each dose level will be administered to up to five 
subjects, starting with  an initial dose of 100 mg/m2, and escalating in 100 mg increments. 
 
Ethical Considerations 
This study will be conducted in accordance with all applicable government regulations 
and University of Arkansas for Medical Sciences research policies and procedures. This 
protocol and any amendments will be submitted and approved by the UAMS Institutional 
Review Board (IRB) to conduct the study. 
The formal consent of each subject, using the IRB-approved consent form, will be 
obtained before that subject is submitted to any study procedure. All subjects for this 
study will be provided a consent form describing this study and providing sufficient 


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information in language suitable for subjects to make an informed decision about their 
participation in this study. The person obtaining consent will thoroughly explain each 
element of the document and outline the risks and benefits, alternate treatment(s), and 
requirements of the study. The consent process will take place in a quiet and private 
room, and subjects may take as much time as needed to make a decision about their 
participation. Participant’s privacy will be maintained and questions regarding  
participation will be answered. No coercion or undue influence will be used in the consent 
process. This consent form must be signed by the subject and the person obtaining the 
consent. A copy of the signed consent will be given to the participant, and the informed 
consent process will be documented in the research record. 
 
Dissemination of Data 
Results of this study may be used for presentations, posters, or publications. The 
publications will not contain any identifiable information that could be linked to a 
participant. The study will be listed on clinicaltrials.gov in accordance with (journal or FDA) 
requirements. 


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