Cytarabine Plus Continuous Infusion Daunorubicin Induction Therapy for Adults With Acute Myeloid Leukemia: A Feasibility Study With Cardiac MRI Monitoring
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Sponsor: Wake Forest University Health Sciences

Cytarabine plus Continuous Infusion Daunorubicin Induction Therapy for Adults with Acute 
Myeloid Leukemia; A Feasibility Study with Cardiac MRI Monitoring 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC 22616 
ClinicalTrials.gov:  NCT02971397
Principal Investigator: 
Co-Investigators: 
Bayard L. Powell, M.D. 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
Leslie R. Ellis, M.D. 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Dianna Howard, M.D. 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Timothy S. Pardee, M.D., Ph.D. 
Section on Hematology and Oncology 
Wake Forest University School of Medicine 
Greg Hundley, MD 
Internal Medicine-Cardiovascular Medicine    
Wake Forest School of Medicine Winston-
Salem, NC 27157 
Susan Lyerly, P.A.-C. 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
Rupali Roy Bhave, MD 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 

Cytarabine plus Continuous Infusion Daunorubicin Induction Therapy for Adults with Acute 
Myeloid Leukemia; A Feasibility Study with Cardiac MRI Monitoring 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC 22616 
Protocol version date: 06/02/2017 
        ii 
Biostatistician: 
Study Nurse: 
Study Coordinator: 
Regulatory Contact: 
Protocol Editor: 
Participating Institution(s): Wake 
Forest Baptist Comprehensive 
Cancer Center 
Version Date:  6/2/2017
Amended:  
Ralph B. D’Agostino, Ph.D. 
Department of Biostatistical Sciences 
Wake Forest School of Medicine 
Winston-Salem, NC 27157 
Sharon Averill, RN 
Comprehensive Cancer Center of 
Wake forest School of Medicine 
Winston-Salem, NC 27157 
Meg Green 
Comprehensive Cancer Center of 
Wake Forest School of Medicine 
Winston-Salem, NC 27157 
Cindy Miller, AAS 
Comprehensive Cancer Center of 
Wake forest School of Medicine 
Winston-Salem, NC 27157 
Mac Robinson, PhD Comprehensive 
Cancer Center of Wake Forest 
School of Medicine Medical Center 
Blvd 
Winston-Salem, NC 27157 
WFBCCC 22616
9/28/16 
06/02/2017 
Confidential

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        3 
Table of Contents 
SCHEMA ................................................................................................................................... 5 
1.0 
Introduction and Background .......................................................................................... 6 
1.1 
Chemotherapy-induced cardiotoxicity ......................................................................... 6 
1.2 
Daunorubicin administration ....................................................................................... 6 
2.0 
Objectives ...................................................................................................................... 7 
2.1 
Primary Objectives ..................................................................................................... 7 
2.2 
Secondary Objectives ................................................................................................. 7 
3.0 
Patient Selection ............................................................................................................ 7 
3.1 
Inclusion Criteria ......................................................................................................... 7 
3.2 
Exclusion Criteria ........................................................................................................ 8 
3.3 
Inclusion of Women and Minorities ............................................................................. 9 
4.0 
Registration Procedures ................................................................................................. 9 
5.0 
Study Outcomes ............................................................................................................10 
5.1 
Primary Outcomes .....................................................................................................10 
5.2 
Secondary Outcomes ................................................................................................10 
6.0 
Treatment Plan ..............................................................................................................11 
6.1 
Treatment Administration ...........................................................................................12 
6.1.1 
Allogeneic Stem Cell Transplant ..........................................................................13 
6.2 
Imaging exams ..........................................................................................................13 
6.3 
Analysis of MRI images .............................................................................................14 
6.4 
General Concomitant Medication and Supportive Care Guidelines ............................14 
6.5 
Duration of Therapy ...................................................................................................14 
6.6 
Duration of Follow Up ................................................................................................14 
7.0 
Dose Modifications ........................................................................................................15 
8.0 
Measurement of Effect ..................................................................................................15 
8.1 
Antitumor Effect .........................................................................................................15 
8.2 
Definitions ..................................................................................................................15 
9.0 
Adverse Events List and Reporting Requirements .........................................................16 
9.1 
Adverse event list for daunorubicin ............................................................................16 
9.2 Adverse event list for cytarabine (CYTOSAR) .................................................................16 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        4 
9.3 
Adverse Event Characteristics ...................................................................................19 
9.4 
STRC SAE Reporting Requirements .........................................................................19 
9.5 
WFUHS IRB AE Reporting Requirements .................................................................19 
10.0 
Pharmaceutical Information ...........................................................................................20 
10.1 
Pharmaceutical Accountability ...................................................................................20 
10.2 
Daunorubicin .............................................................................................................20 
10.3 
Cytarabine .................................................................................................................21 
12.0 
Data Management .........................................................................................................21 
13.0 
Statistical Considerations ..............................................................................................21 
13.1 
Analysis of Primary Objective ....................................................................................21 
13.2 
Analysis of Secondary Objective ...............................................................................22 
13.3 
Power and Sample Size ............................................................................................22 
13.4 
Estimated Accrual Rate .............................................................................................22 
13.5 
Estimated Study Length .............................................................................................22 
References ...............................................................................................................................23 
Appendix A – Protocol Registration Form ..................................................................................24 
Appendix B – Subject Eligibility Checklist ..................................................................................25 
Appendix C – Mandatory STRC SAE Reporting Guidelines ......................................................28 
Appendix D - Response Criteria14 .............................................................................................32 
Appendix E: Cardiac Function Worksheet .................................................................................33 
Appendix F – Adverse Event Log ..............................................................................................35 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        5 
1. SCHEMA
Consent and pre-study data collection 
Induction: Daunorubicin via continuous infusion 
Baseline Troponin I, ECHO (full), MRI 
Day 1-7: Cytarabine 100 mg/m2/day 
Day 1-3: Daunorubicin 60 mg/m2/day 
Day 14 (± 2): Bone marrow biopsy 
Study follow-up 
•
MRI/ECHO at 3 months or relapse
•
MRI at 6 months or relapse
Cycle 1 
Day 1-5: Cytarabine 100 mg/m2/day 
Day 1-2: Daunorubicin 60 mg/m2/day 
Day 3: Troponin I 
Consolidation 
therapy  
High dose Cytarabine (Days 1, 3, 5; up to 3 cycles, 
or up to 4 cycles for CBF AML) 
•
< 60 years: 3,000 mg/m2/day
•
≥ 60 years: 1,500 mg/m2/day
Day 4: Troponin I 
For patients requiring re-induction 
Day 14 (± 2):  Bone marrow biopsy 
ECHO (limited, with strain 
measures) 
Cycle 2 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        6 
1.0  Introduction and Background 
It is estimated that 19,950 people will be diagnosed with acute myeloid leukemia (AML) 
and 10,430 will die from it in the United States in 2016.1 Standard induction therapy for 
patients with good performance status consists of a 7+3 regimen of cytarabine 100-200 
mg/m2 continuous infusion x 7 days with an anthracycline, i.e. daunorubicin 60-90 mg/m2 
(45-90 mg/m2 for patients ≥60 years or idarubicin 12 mg/m2) x 3 days.2 While advances 
in treatment have resulted in substantially improved complete remission (CR) rates, with 
60% to 70% of adults expected to attain CR status following appropriate induction 
therapy, only slightly more than 25% (about 45% of those who attain CR) can be 
expected to survive 3 or more years. 
1.1 
Chemotherapy-induced cardiotoxicity 
Along with myelosuppression, cardiac effects are the key dose-limiting toxicities of 
daunorubicin and other drugs in the anthracyclines class. Treatment with daunorubicin 
can result in arrhythmias and cardiomyopathy, with a maximum total (lifetime) dose of 
500-600 mg/m2 recommended because of cumulative cardiotoxicity. Currently there is
no reliable method of predicting patients at increased risk for developing cardiotoxicity.
Transthoracic echocardiography is used most widely to measure cardiac function and
volume because of its availability, anatomic and prognostic validation, and lack of
ionizing radiation.3-5 Furthermore, when cardiac chambers contract in a uniform and
symmetric pattern, a close correlation is found between echocardiographic and
angiographic volume measurements.6 Limitations of echocardiography include difficulty
in assessing the apex and right ventricle. In addition, assumptions regarding the
geometry of the LV (as a prolate ellipsoid) are used to estimate ventricular volumes and
mass. MRI acquires tomographic 2D or 3D images of the entire heart. Volumetric
assessment of the LV is independent of geometric assumptions, noninvasive, and free of
exposure to contrast agents or ionizing radiation. MRI is considered superior to other
imaging techniques because of its capability for high-resolution measurements of
anatomy and function of the LV.7 Cardiac MRI was successfully implemented in the
Multi-Ethnic Study of Atherosclerosis (MESA), sponsored by the National Heart, Lung,
and Blood Institute of the National Institutes of Health.8
1.2 
Daunorubicin administration 
Previous studies in patients with advanced breast and ovarian cancer and metastatic 
soft tissue sarcoma have examined cardiotoxicity outcomes with bolus versus 
continuous infusion administration of anthracyclines and found a decreased risk with 
continuous infusion.9-11 A Southwest Oncology Group study in AML patients included 
infusional daunorubicin and cytarabine with and without cyclosporin and concluded that 
infusional daunorubicin did not significantly alter the toxicity profile or efficacy of the 
standard 7+3 regimen, although, this was not the main objective of the study.12 
There is limited but sufficient evidence to suggest that daunorubicin administered as a 
continuous infusion rather than bolus in the standard 7+3 regimen would provide a 
reduced risk of cardiotoxic effects with at least similar response rates. As such, this 
study aims to assess the safety and feasibility of administering daunorubicin as a 
continuous infusion in patients undergoing induction therapy for newly diagnosed AML. 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        7 
We will assess clinical outcomes under the proposed regimen, as well as examine the 
use of cardiac MRI in identifying cardiac toxicity. 
2.0 
Objectives 
2.1 
Primary Objectives 
2.1.1 To assess the safety (at 3 months) and feasibility of administering 
daunorubicin as continuous infusion under the proposed treatment 
regimen. 
2.2 
Secondary Objectives 
2.2.1 To assess the safety (at 6 months) of administering daunorubicin as 
continuous infusion under the proposed treatment regimen. 
2.2.2 To assess treatment outcomes (including CR and CRi) in patients with 
AML under the proposed treatment regimen. 
2.2.3 To compare the concordance between MRI and ECHO in identifying 
cardiac toxicity, i.e. a reduction in LVEF of ≥10% and EF≤50% compared 
to baseline LVEF. 
3.0 
Patient Selection 
3.1 
Inclusion Criteria 
3.1.1 
Patients must have morphologically confirmed newly diagnosed acute 
myelogenous leukemia (AML) with blood or bone marrow disease. Patients 
with only extramedullary disease in the absence of bone marrow or blood 
involvement are eligible. Note: This protocol uses WHO diagnostic criteria for 
AML. Patients with acute promyelocytic leukemia (APL, FAB, M3) or blastic 
transformation of chronic myelogenous leukemia (CML) are not eligible. 
3.1.2 
≥ 18 years of age. 
3.1.3 
ECOG performance status 0-3. 
3.1.4 
Patients with ECHO EF ≥ 45% within 28 days prior to registration. 
3.1.5 
Because of the teratogenic potential of the drugs used in this study, women 
of child-bearing potential and men must agree to use adequate contraception 
(hormonal or barrier method of birth control; abstinence) prior to study entry 
and for the duration of study participation. Should a woman become pregnant 
or suspect she is pregnant while participating in this study, she should inform 
her treating physician immediately. 
3.1.6 
Ability to understand and the willingness to sign an IRB-approved informed 
consent document. 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        8 
3.2 
Exclusion Criteria 
3.2.1 
Patients who have received prior induction chemotherapy for AML or MDS. 
Temporary prior measures such as apheresis or hydroxyurea are allowed. 
Patients who have received a limited and short-term exposure of ATRA (all 
trans retinoic acid) while AML-M3 (Acute Promyelocytic Leukemia) was being 
ruled out, and which has been discontinued, will be eligible.   
3.2.2 
Patients receiving any other investigational agents. 
3.2.3 
Patients with prolonged QTc interval (> 500 msec) determined by EKG within 
28 days prior to registration. 
3.2.4 
Patients not suitable for cardiac MRI. Contraindications include: 
•
Intracranial metal, pacemakers, defibrillators, functioning neurostimulator
devices, or other implanted electronic devices
•
Ferromagnetic cerebral aneurysm clips, or other intraorbital/intracranial
metal
•
Allergy to Gadolinium or other severe drug allergies
•
Claustrophobia
•
Congestive heart failure (NYHA class III or IV)
•
Significant valvular disease, or significant pulmonary disease requiring
supplemental oxygen therapy
3.2.5 
History of allergic reactions attributed to compounds of similar chemical or 
biologic composition to daunorubicin or cytarabine. 
3.2.6 Patients with documented CNS involvement. 
3.2.7 
Patients who are known to be HIV+ may be eligible providing they meet all of 
the following additional criteria within 28 days prior to registration: 
• CD4 cells ≥ 500/mm3
• Viral load of < 50 copies HIV mRNA/mm3 if on cART or < 25,000 copies
HIV mRNA if not on cART 
• No zidovudine or stavudine as part of cART
Patients who are HIV+ and do not meet all of these criteria are not eligible for 
this study. 
3.2.8 
Patients with other uncontrolled intercurrent illness or psychiatric 
illness/social situations that would limit compliance with study requirements. 
3.2.9 
Pregnant women are excluded from this study because of the potential for 
teratogenic or abortifacient effects with drugs used in this study. Because 
there is an unknown but potential risk for adverse events in nursing infants 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        9 
secondary to treatment of the mother with the drugs used in this study, 
breastfeeding should be discontinued prior to beginning treatment. 
3.3 
Inclusion of Women and Minorities 
Men and women of all races and ethnicities who meet the above-described 
eligibility criteria are eligible to participate in this study.  
The study consent form will also be provided in Spanish for Spanish-speaking 
participants. Based on WFBCCC population estimates, we expect approximately 
44% of participants to be women. Translating this to our sample size estimate of 
40, we plan to enroll at least 18 women. Similarly, we expect approximately 3% 
of study participants to be Hispanic/Latino (N=1). We plan to enroll at least 11% 
Black or African American (N=4), 0% American Indian/Alaska Native (N=0), 
.006% Asian (N=1). Should we not meet or exceed these estimates, the PI will 
engage the Cancer Center Health Equity Advisory Group to discuss strategies to 
enhance recruitment in these target populations. 
4.0 
Registration Procedures 
All patients entered on any WFBCCC trial, whether treatment, companion, or cancer control 
trial, must be registered with the WFBCCC Protocol Registrar or entered into ORIS Screening 
Log within 24 hours of Informed Consent. Patients must be registered prior to the initiation of 
treatment.   
You must perform the following steps in order to ensure prompt registration of your patient: 
1. Complete the Eligibility Checklist (Appendix B)
2. Complete the Protocol Registration Form (Appendix A)
3. Alert the Cancer Center registrar by phone, and then send the signed Informed
Consent Form, Eligibility Checklist and Protocol Registration Form to the registrar,
either by fax or e-mail.
Contact Information: 
Protocol Registrar PHONE (336) 713-6767 
Protocol Registrar FAX (336) 713-6772 
Protocol Registrar E-MAIL (registra@wakehealth.edu)  
*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday.
4. Fax/e-mail ALL eligibility source documents with registration. Patients will not be
registered without all required supporting documents.
Note: If labs were performed at an outside institution, provide a printout of the results. 
Ensure that the most recent lab values are sent. 
To complete the registration process, the Registrar will:  
•
assign a patient study number
•
register the patient on the study

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        10 
5.0 
Study Outcomes 
5.1 
Primary Outcomes 
5.1.1 Cardiac toxicity(see 2.2.3), as measured by MRI (ejection fraction [EF], 
left ventricular end diastolic volume [LVEDV], left ventricular end systolic 
volume [LVESV], T1/T2 mapping and myocardial strain) measures and 
ECHO (EF, myocardial strain, LVEDV, LVESV, ESV, mitral inflow E, A, E’ 
and A’) measures.  Cardiac toxicity is defined as reduction in LVEF of 
≥10% compared to baseline LVEF and EF≤50% on the follow-up scan. 
This assessment will be performed using both an ECHO and MRI 
measure.  In addition, the primary outcome will be assessed at the 3 
month follow-up (or relapse) visit. 
5.1.2 Other unexpected toxicities (exclude hematologic and infectious) ≥ grade 
3, as measured by CTCAE v 4.0 
5.1.3 Feasibility, as measured by ability to administer continuous infusion 
daunorubicin and complete required study assessments with limited 
deviation from the proposed regimen (as defined in section 8.2)  
5.2 
Secondary Outcomes 
5.2.1 Cardiac toxicity(see 2.2.2), as measured by MRI (ejection fraction [EF], 
left ventricular end diastolic volume [LVEDV], left ventricular end systolic 
volume [LVESV], T1/T2 mapping and myocardial strain) measures and 
ECHO (EF, myocardial strain, LVEDV, LVESV, ESV, mitral inflow E, A, E’ 
and A’) measures.  Cardiac toxicity is defined as reduction in LVEF of 
≥10% compared to baseline LVEF and EF≤50% on the follow-up scan. 
This assessment will be performed using both an ECHO and MRI 
measure.  In addition, these secondary outcomes will be assessed at the 
6 month follow-up (or relapse) visit 
5.2.2 Treatment outcomes (such as overall response rate) stratified by age 
(≥60, < 60) and ECOG (0-2, 3): Overall response rate (CR + CRi); 
Induction death rate; Presence of persistent leukemia; Disease-free 
survival (for those who achieve remission) 
5.2.3 Measures of ECHO and MRI derived measures of EF, myocardial strain, 
LVEDV and LVESV. 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC MRI MONITORING, INDUCTION 
THERAPY FOR ADULTS WITH ACUTE MYELOID LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        11 
6.0 
Treatment Plan 
Study 
entrya 
INDUCTI
ON: 
(up to 2 
Cycles) 
*At each
treatment
* 
INDUCTION CYCLE 1 
*Additional Activities*
INDUCTION CYCLE 2  
 (**if needed as indicated by 
bone marrow aspirate and 
biopsy) 
*Additional Activities*
CONSOLIDATION
: (up to 4 Cycles 
for CBF AML) 
*At each
treatment*
Post- 
treatment 
Follow-up or 
relapse 
Day 4 
Day 14 (+/- 2 
days) 
Prior 
Day 3 
Day 14 (+/- 2 
days) 
3 mos. 
6 mos 
Informed consent 
X 
Demographics 
X 
Medical history 
X 
Concurrent meds 
X 
Physical exam 
X 
Vital signs 
X 
X 
X 
Height, Weight, M2 
X 
Performance Status 
X 
Bone marrow aspirate & 
biopsyb
X 
Xb
Xb
Xb 
CBC w/diff, platelets 
X 
X 
X 
X 
Serum chemistryc 
Xd
X 
X 
Troponin I (Appendix E) 
Xd
Xe 
Xe 
B-HCGf
X 
ECHO (Appendix E) 
Xh
Xg 
Xg
MRI without contrast 
(Appendix E) 
X 
X 
X 
Adverse event 
evaluation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a Completed within 28 days prior to registration unless otherwise indicated. 
b On day 14 (+2 days) of Induction Cycles 1 and 2, at recovery to confirm response, and at completion of all treatment, then as clinically indicated. 
c Total bilirubin, BUN, creatinine,  SGOT[AST], SGPT[ALT] 
d Draw after consent signed and prior to day 1 treatment; results not required to start treatment. 
e On day 4 of treatment of Induction Cycle 1, and on day 3 of Induction Cycle 2 for those with persistent leukemia. 
f Serum pregnancy test (women of childbearing potential). 
g Limited ECHO with strain measures  
h Full 3D ECHO

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        12 
6.1 
Treatment Administration 
Treatment will be administered on an inpatient basis. Reported adverse events and 
potential risks are described in Section 9. No investigational or commercial agents or 
therapies other than those described below may be administered with the intent to treat 
the patient's malignancy. 
Agent 
Dose 
Route 
Schedule 
Cycle 
Length 
Induction 
Cytarabine 
100 mg/m2/day 
IV infusion 
Days 1-7 
14 days 
Daunorubicin 
60 mg/m2/day 
IV infusion 
Days 1-3 
Re-induction (if needed) 
Cytarabine 
100 mg/m2/day 
IV infusion 
Days 1-5 
14 days 
Daunorubicin 
60 mg/m2/day 
IV infusion 
Days 1-2 
Consolidation (up to 3 cycles, or up to 4 cycles for CBF AML) 
Cytarabine 
 <60 yrs: 3,000 
mg/m2/day 
≥ 60 yrs: 1,500 
mg/m2/day 
IV infusion over 3 hours, 
every 12 hours 
Days 1,3,5 
≥ 28 days 
Induction: This study regimen will follow the standard 7+3 regimen of cytarabine and 
daunorubicin, with the modification of daunorubicin administered as continuous infusion 
rather than bolus. Baseline troponin I, full 3D ECHO, and MRI without contrast will be 
performed prior to treatment.  
For troponin determination, the study will use either the TnI-Ultra™ assay, Siemens, 
Munich Germany or the Beckman Coulter Access 2 AccuTnI+3 assay for detection of 
troponin I. While the assays are comparable, every effort will be made to test all samples 
on the current Institutional standard troponin I testing platform (TnI-Ultra assay, 
Siemens). If the TnI-Ultra assay becomes unavailable either because of changing 
Institutional standards or product availability the Beckman Coulter Access 2 AccuTnI+3 
assay will be utilized. The brand of assay and results will be recorded for each test on 
the Cardiac Function Worksheet. 
Patients will have a bone marrow aspirate and biopsy on day 14 (+2 days). 
Re-induction: A second induction course may be given if the day 14 bone marrow 
aspirate and biopsy shows bone marrow cellularity as ≥10% and  >5% leukemic 
blasts. Those requiring re-induction will undergo a limited ECHO with strain 
measures prior to treatment. This abbreviated cycle will consist of cytarabine on 
days 1-5 and daunorubicin on days 1 and 2, with a troponin I measure on day 3 
and a bone marrow biopsy on day 14 (+2 days). Patients not achieving a 
remission after 2 induction attempts will be removed from study. 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        13 
Patients without bone marrow involvement at diagnosis will receive a second 
induction course if they have not cleared their soft tissue disease by day 14 (± 2 
days). 
If cellularity is <10% on day 14, a repeat bone marrow biopsy should be obtained as 
clinically indicated. Treatment response will be evaluated once ANC >1,000 /µL and 
platelets >100,000/µL, but no later than day 42. If peripheral blood counts are 
inadequate (ANC<1,000/μL, platelets<100,000/μL) at the time of this bone marrow 
aspirate and biopsy, a repeat bone marrow aspirate and biopsy must be obtained to 
document complete remission at the time of peripheral blood count recovery 
(ANC≥1,000/μL, platelets≥100,000/μL) if > 1 week after “day 42” bone marrow study. 
Physicians should consider earlier bone marrow exams in patients whose peripheral 
blood counts are not recovering or recovering sluggishly, as well as in patients whose 
day 14 bone marrow was suspicious for residual leukemia. 
Consolidation: Patients in remission will receive high-dose cytarabine (days 1, 3, and 5) 
consolidation therapy for up to 3 cycles (except in the case of toxicity or receipt of stem 
cell transplant). Patients with core-binding factor (CBF) AML may receive 4 cycles of 
consolidation therapy. Therapy should be started as soon as possible (and within 14 
days) after recovery from induction/re-induction therapy.  
6.1.1  Allogeneic Stem Cell Transplant 
Patients with intermediate and high-risk disease by cytogenetics and/or molecular 
studies should be considered for allogeneic transplant while in first remission. The 
transplantation, including donor selection, will not be guided by this protocol but will 
be at the discretion of the treating physician. 
6.1.2  Positive for FLT-3 
Patients found to be positive for FLT-3 may have midostaurin added to induction and 
consolidation per approved indications 
6.2 
Imaging exams 
Upon enrollment, subjects will be scheduled for the echocardiogram, cardiac MRI exam 
and clinic visit for labwork. For the Ultrasound portion of the study, the subject will go to 
the Clinical Ultrasound lab. After arrival at the ultrasound lab, the subject will be 
positioned on a scanning bed with ECG leads attached. Then an ultrasound transducer 
will be placed on the subject’s chest and pictures will be taken of the heart using three-
dimensional imaging and spectral Doppler techniques. The total time of the ultrasound 
testing will be 45 minutes. The MRI exam will be performed in the CMR suite where they 
will be placed supine on the CMR table and ECG leads and respiratory gating bellows 
applied. CMR scans will be performed on a 1.5 Tesla GE CVi scanner with a phased 
array surface coil applied around the chest to optimize signal to noise. All images will be 
acquired using a fast gradient echo technique, with the repetition time (TR) and echo 
time (TE) based on the R-R interval of the subject. Multi-slice coronal, gradient echo 
sequences will be used to obtain scout images of the chest and locate the left ventricle. 
After locating the LV a series of steady state free precession, short axis views will be 

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acquired perpendicular to the left ventricle covering from the base to the apex; imaging 
parameters were 32cm field of view, 35˚ flip angle, 8mm slice thickness, 2mm inter-slice 
space, and a 256X128 matrix. These scans will incorporate a temporal resolution of 
40msec in order to identify end-systole for the determinations of LV volumes, EF, and 
mass. This protocol will be identical to that implemented in CCWFU 98998 and the Multi-
Ethnic Study of Atherosclerosis.13 
6.3 
Analysis of MRI images 
For LV mass, volume, and EF determinations, calculations will be performed according 
to widely published and currently accepted techniques that are in current use at or 
institution in single and multi-center trials. The epi- and endocardial border of each slice 
from the multi automated drawing program, and assessments will be calculated by 
summation (Simpson’s rule).  Basal slices will be reviewed in cine format to resolve 
structures for inclusion (the aortic outflow tract) or exclusion (left atrium and mitral 
leaflets) from the mass, volume, and EF measurements.  
6.4 
General Concomitant Medication and Supportive Care 
Guidelines 
Patients should receive full supportive care, including transfusions of blood and blood 
products, erythropoietin, antibiotics, antiemetics, etc., as clinically indicated. Anti-
inflammatory or narcotic analgesics may be offered as needed. Medications considered 
necessary for the patient's well-being may be given at the discretion of the investigator, 
i.e., chronic treatments for concomitant medical conditions, as well as agents required
for life-threatening medical problems, etc. The reason(s) for treatment, dosage, and
dates of treatment should be recorded on the flow sheets.
6.5 
Duration of Therapy 
Treatment under this protocol may continue until one of the following criteria applies: 
•
Allogeneic stem cell transplant,
•
Disease progression,
•
Intercurrent illness that prevents further administration of treatment,
•
Unacceptable adverse event(s),
•
Patient decides to withdraw from the study, or
•
General or specific changes in the patient's condition render the patient
unacceptable for further treatment in the judgment of the investigator.
6.6 
Duration of Follow Up 
Patients will have an MRI without contrast and full/limited ECHO at 3 months or relapse, 
whichever occurs first. Patients still on protocol at 6 months post-treatment will have an 
MRI without contrast only. 
Patients will be followed for a minimum of 30 days after the last study drug is 
administered or until death, whichever occurs first, for adverse events monitoring. 
Patients removed from the study for unacceptable adverse events will be followed until 
resolution or stabilization of the adverse event. 

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Patients will be followed by phone call every 3 months for monitoring survival endpoints. 
7.0 
Dose Modifications 
Induction: no dose reductions allowed. 
Re-induction: Dose reductions may be allowed in the setting of hepatotoxicity as follows: 
•
For SGPT/SGOT 150-300 U/L OR bilirubin 1.5-3.0 mg/dL, reduce daunorubicin
dose to 45 mg/m2/day.
•
For SGPT/SGOT > 300 U/L OR bilirubin > 3.0-5.0 mg/dL, reduce daunorubicin
dose to 30 mg/m2/day.
Consolidation: No dose reductions allowed for Cycle 1 except in the instance of renal 
dysfunction, as follows: 
•
For creatinine greater than 2 mg/dL or calculated creatinine clearance of < 50
mL/min, decrease cytarabine dose to 1,000 mg/m2/dose.
•
For creatinine greater than 3 mg/dL or calculated creatinine clearance of < 30
mL/min, change cytarabine to 400 mg/m2/day IV infusion over 24 hours daily for
5 days.
For consolidation cycles beyond Cycle 1, doses of cytarabine may be reduced by 750 
mg/m2/day for the following reasons: 
•
Grade 3-4 non-hematologic toxicity
•
Severe life-threatening infection
If toxicity persists, cytarabine dose may be reduced by an additional 750 mg/m2/day. 
 8.0 Measurement of Effect 
8.1 
Antitumor Effect 
Response and progression will be evaluated in this study criteria defined by 
Cheson et al.14 (see Appendix D). 
8.2 
Definitions 
•
Study Regime: Completion of the critical study regime tasks will be tracked by
research staff and recorded as “Yes” or “No” in Appendix E, The Cardiac
Function form. The tasks that should be recorded in this manner are the
following:
•
The daunorubicin infusion (Induction):
o
if this is not completed in 72 hours +/- 1,  record as “No”,
o
If the infusion in completed within these parameters record “yes”.

If “No”, record the total infusion amount and time taken to
administer.

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•
ECHO (at pre-induction visit, *post-treatment (pre-discharge), 3 month follow-up
or relapse):
o
Record “Yes” or “No” if the patient completes or does not complete the
ECHO at each visit.
o
*indicates an additional assessment for those individuals requiring a
second cycle of Induction therapy
•
MRI (at pre-induction visit, 3 month follow-up or relapse, at 6 month follow-up or
relapse):
o
Record “Yes” or “No” if the patient completes or does not complete the
MRI at each visit.
•
Evaluable for toxicity: All patients will be evaluable for toxicity from the time of
their first treatment with daunorubicin.
•
Persistent leukemia: Patients not achieving a remission after 2 induction
attempts; these patients will be removed from the study.
•
Disease-free survival: calculated for patients who achieve CR and measured
from the date of CR until relapse from CR or death. Observation is censored at
the date of last follow-up for patients last known to be alive without report of
relapse.
•
Time to death: calculated from date of study registration to date of death due to
any cause. Patients last known to be alive are censored at date of last contact.
9.0 
Adverse Events List and Reporting Requirements 
9.1 
Adverse event list for daunorubicin 
Acute myelosuppression is the dose limiting side effect, with the greatest effect 
on the granulocytic series. In addition, daunorubicin causes alopecia, and 
nausea and vomiting in a significant number of patients treated. Extravasation of 
daunorubicin can cause severe local tissue necrosis. There is increased potential 
for cumulative-dose-related cardiomyopathy with congestive heart failure. 
9.2   Adverse event list for cytarabine (CYTOSAR) 
Conventional Dose Therapy Table 1 - Adverse Reactions (with conventional dose 
therapy): The reported adverse reactions are listed below by MedDRA System Organ Class 
and by frequency. Frequencies are defined as: Very common (>10%), Common (>1%, 
≤10%), Uncommon (>0.1%, ≤1%), Rare (>0.01%, ≤0.1%), and Frequency not known 
(cannot be estimated from available data).  
Blood and Lymphatic System Disorders: 
Very common 
Bone marrow failure, thrombocytopenia, 
anaemia, anaemia megaloblastic, 
leukopenia, reticulocyte count decreased 
Frequency not known 
Bleeding (all sites) 
Cardiac Disorders: 
Frequency not known 
Pericarditis 
Eye Disorders: 
Frequency not known 
Conjunctivitis
a 

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Gastrointestinal Disorders: 
Very common 
Stomatitis, mouth ulceration, anal ulcer, anal 
inflammation, diarrhea, vomiting, nausea, 
abdominal pain 
Frequency not known 
Bowel necrosis, Pancreatitis, oesophageal 
ulcer, oesophagitis 
General Disorders and Administration Site Conditions: 
Very common 
Pyrexia 
Frequency not known 
Chest pain, injection site reaction
b
Hepatobiliary Disorders: 
Very common 
Hepatic function abnormal 
Frequency not known 
Jaundice 
Infections and Infestations: 
Very common 
Sepsis, pneumonia, infection
c
Frequency not known 
Injection site cellulitis 
Immune System Disorders: 
Frequency not known 
Anaphylactic reaction, allergic oedema 
Investigations: 
Very common 
Biopsy bone marrow abnormal, blood smear 
test abnormal 
Metabolism and Nutrition Disorders: 
Frequency not known 
Decreased appetite 
Musculoskeletal, Connective Tissue and Bone Disorders: 
Very common 
Cytarabine syndrome 
Nervous System Disorders: 
Frequency not known 
Neurotoxicity, neuritis, dizziness, headache 
Renal and Urinary Disorders: 
Frequency not known 
Renal impairment, urinary retention 
Respiratory, Thoracic and Mediastinal Disorders: 
Frequency not known 
Dyspnoea, oropharyngeal pain 
amay occur with rash and may be hemorrhagic with high dose therapy 
bpain and inflammation at subcutaneous injection site 
c may be mild, but can be severe and at times fatal  
High Dose Therapy 
Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with 
conventional therapy regimens of CYTOSAR(cytarabine) has been reported following high 
dose schedules (2.0 g to 3.0 g/m2 given every 12 hours for 12 doses). Table 2: Adverse 
Reactions (with High Dose Therapy): The reported adverse reactions are listed below by 
MedDRA System Organ Class and by frequency. Frequencies are defined as: Very common 
(>10%), Common (>1%, ≤10%), Uncommon (>0.1%, ≤1%), Rare (>0.01%, ≤0.1%), and 
Frequency not known (cannot be estimated from available data).  
Cardiac Disorders: 
Frequency not known 
Cardiomyopathy
a 

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Eye Disorders: 
Very common 
Corneal disorder 
Frequency not known 
hemorrhagic conjunctivitis
b 
Gastrointestinal Disorders: 
Common 
Necrotizing colitis 
Frequency not known 
Gastrointestinal necrosis, gastrointestinal 
ulcer, pneumatosis intestinalis, peritonitis 
Hepatobiliary Disorders: 
Frequency not known 
Liver injury, hyperbilirubinaemia 
Infections and Infestations: 
Very common 
Sepsis 
Frequency not known 
Liver abscess 
Nervous System Disorders: 
Very common 
Cerebral disorder, cerebellar disorder, 
somnolence 
Frequency not known 
Coma, convulsion, peripheral motor 
neuropathy, peripheral sensory neuropathy 
Psychiatric Disorders: 
Frequency not known 
Personality change
c 
Respiratory, Thoracic and Mediastinal Disorders: 
Very common 
Acute respiratory distress syndrome, 
pulmonary oedema 
Skin and Subcutaneous Tissue Disorders: 
Common 
Skin exfoliation, 
aWith subsequent death 
b may be prevented or diminished by prophylaxis with a local corticosteroid eyedrop  
c Personality change was reported in association with cerebral and cerebellar dysfunction. 
Peripheral motor and sensory neuropathies after consolidation with high-dose CYTOSAR, 
daunorubicin, and asparaginase have occurred in adult patients with acute non lymphocytic 
leukemia. Patients treated with high-dose CYTOSAR should be observed for neuropathy since 
dose schedule alterations may be needed to avoid irreversible neurologic disorders.  
Corneal toxicity consisting of ocular pain, tearing, foreign-body sensation, photophobia and 
blurred vision has been reported. 
Rarely, severe skin rash, leading to desquamation has been reported. Complete alopecia is 
more commonly seen with high dose therapy than with standard CYTOSAR treatment 
programs.  
If high dose therapy is used, do not use a diluent containing benzyl alcohol. 

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Intermediate dose therapy  
A diffuse interstitial pneumonitis without clear cause that may have been related to Cytosar was 
reported in patients treated with experimental intermediate doses of CYTOSAR (1 gm/m
2 ) with
and without other chemotherapeutic agents (meta-AMSA, daunorubicin, VP-16). 
9.3 
Adverse Event Characteristics 
•
CTCAE term (AE description) and grade:  The descriptions and grading
scales found in the revised NCI Common Terminology Criteria for Adverse
Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate
treatment areas should have access to a copy of the CTCAE version 4.0. A
copy of the CTCAE version 4.0 can be downloaded from the CTEP web site
(http://ctep.cancer.gov).
•
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1
above) for expedited reporting purposes only.
•
Attribution of the AE:
-
Definite – The AE is clearly related to the study treatment.
-
Probable – The AE is likely related to the study treatment.
-
Possible – The AE may be related to the study treatment.
-
Unlikely – The AE is doubtfully related to the study treatment.
-
Unrelated – The AE is clearly NOT related to the study treatment.
9.4 
STRC SAE Reporting Requirements 
The Safety and Toxicity Reporting Committee (STRC) is responsible for reviewing SAEs 
for WFBCCC Institutional studies as outlined in Appendix B. STRC currently requires 
that all unexpected 4 and all grade 5 SAEs on these trials be reported to them for 
review. All WFBCCC Clinical Research Management (CRM) staff members assisting a 
Principal Investigator in investigating, documenting and reporting an SAE qualifying for 
STRC reporting are responsible for informing a clinical member of the STRC as well as 
the entire committee via the email notification procedure of the occurrence of an SAE. 
9.5  
WFUHS IRB AE Reporting Requirements 
Any unanticipated problems involving risks to subjects or others and adverse events 
shall be promptly reported to the IRB, according to institutional policy. Reporting to the 
IRB is required regardless of the funding source, study sponsor, or whether the event 
involves an investigational or marketed drug, biologic or device. Reportable events are 
not limited to physical injury, but include psychological, economic and social harm. 
Reportable events may arise as a result of drugs, biological agents, devices, procedures 
or other interventions, or as a result of questionnaires, surveys, observations or other 
interactions with research subjects. 
All members of the research team are responsible for the appropriate reporting to the 
IRB and other applicable parties of unanticipated problems involving risk to subjects or 
others. The Principal Investigator, however, is ultimately responsible for ensuring the 

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prompt reporting of unanticipated problems involving risk to subjects or others to the 
IRB. The Principal Investigator is also responsible for ensuring that all reported 
unanticipated risks to subjects and others which they receive are reviewed to determine 
whether the report represents a change in the risks and/or benefits to study participants, 
and whether any changes in the informed consent, protocol or other study-related 
documents are required. 
Any unanticipated problems involving risks to subjects or others occurring at a site 
where the study has been approved by the WFUHS IRB (internal events) must be 
reported to the WFUHS IRB within 7 calendar days of the investigator or other members 
of the study team becoming aware of the event. 
Any unanticipated problems involving risks to subjects or others occurring at another site 
conducting the same study that has been approved by the WFUHS IRB (external 
events) must be reported to the WFUHS IRB within 7 calendar days of the investigator 
or other members of the study team becoming aware of the event. 
Any event, incident, experience, or outcome that alters the risk versus potential benefit 
of the research and as a result warrants a substantive change in the research protocol or 
informed consent process/document in order to insure the safety, rights or welfare of 
research subjects. 
10.0 Pharmaceutical Information 
10.1 Pharmaceutical Accountability 
The drugs used in this study regimen, daunorubicin and cytarabine, are 
commercially available. 
10.2 Daunorubicin 
Product description:  Anthracycline. Commercially available in 20 mg and 50 
mg glass vials of red colored lyophilized drug.  
Solution preparation: Each 20 mg vial is reconstituted with 4 mL of sterile water 
to give a final concentration of 5 mg/mL. 
Storage and stability:  Intact vials are stored at room temperature and protected 
from direct sunlight. Reconstituted solutions are stable for 48 hours when 
refrigerated at 2°–8°C (36°–46°F) and 24 hours at room temperature, when 
protected from sunlight. Do not freeze.  
Route of administration:  Continuous intravenous infusion over 24 hours. 
Compatible with cytarabine. Incompatible with sodium heparin. Vesicant. 
Disposal: Care should be taken in disposing daunorubicin. Daunorubicin is a 
vesicant; wear proper protective equipment when handling. Dispose of per local 
regulations and the Wake Forest Hem/Onc Waste Disposal Guide.  

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10.3 Cytarabine 
Product description:  Antimetabolite. Commercially available in 100 mg, 500 
mg, 1 gm, and 2 gm vials. 
Solution preparation: For IV use, reconstitute the 100 mg vial with 5 mL 
bacteriostatic water for injection to achieve a concentration of 20 mg/mL. Add 10 
mL of bacteriostatic water to the 500 mg vial to achieve a final concentration of 
50 mg/mL. Add 10 and 20 mL of bacteriostatic water to the 1 and 2 gm vials 
respectively to achieve a final concentration of 100 mg/mL. 
Storage and stability:  The dry powder is stored at room temperature. Solutions 
reconstituted with sterile water without preservative should be used immediately; 
solutions reconstituted with Bacteriostatic of Water are stable up to 48 hours at 
controlled room temperature (15o to 30oC). Solutions with a slight haze should be 
discarded. 
Route of administration:  Continuous intravenous infusion over 24 hours. 
Disposal: Care should be taken in disposing cytarabine. Dispose of per local 
regulations and the Wake Forest Hem/Onc Waste Disposal Guide.  
12.0 Data Management 
Informed consent document 
ORIS 
Protocol registration form 
ORIS 
Subject Eligibility 
ORIS 
Treatment response form (Appendix D) 
REDCap 
Cardiac function worksheet (Appendix E) 
REDCap 
Adverse events log (Appendix F) 
ORIS 
13.0 Statistical Considerations 
13.1 Analysis of Primary Objective 
Since this is a pilot study, several descriptive analyses will be performed. These 
will include examining the change in each measure of cardiotoxicity from the 
initial pre-chemotherapy assessment to each of the available post-chemotherapy 
imaging assessment (i.e. EF, LVEDV, LVESV, T1/T2 mapping, myocardial 
strain). These comparisons will be made using paired T-tests. Similar analyses 
will be performed using the ECHO-derived measures.  In addition to examining 
the continuous changes in measures, we will determine the proportion of patients 
who exhibit a cardio-toxic event at 3-months defined as have a reduction in 
LVEF≥10% and EF≤50% when compared to baseline.  This event will be defined 
for both the ECHO and MRI measures.  In addition to point estimates of these 
rates, 95% confidence intervals will be calculated.  
Additional toxicity measures will be tabulated after each visit. 

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For feasibility assessment, we will determine the proportion of patients with 
study-related deviations and report these proportions with 95% confidence 
intervals.  In addition, we will determine the proportion of patients who complete 
the infusion therapy. 
13.2 Analysis of Secondary Objective 
Similar toxicity analyses as described above for the primary objective will be 
examined at the 6-month time point. 
We will report frequencies of response status (Overall response rate [CR + CRi]; 
Induction death rate; Percentage of patients with persistent leukemia; Disease-
free survival [for those who achieve remission]) with the number of patients in 
each category of response. Treatment outcomes will be stratified by age (≥60, < 
60),ECOG (0-2, 3), cytogenetic risk groups and prior hematological disease (e.g. 
MDS, MPN). 
Three sets of correlation analyses will be performed; the first will determine the 
correlation between ECHO and MRI assessments performed pre-chemotherapy; 
the second will assess correlations between post-chemotherapy ECHO and MRI 
assessments; and the third will assess correlations between each of the time 
points.  In addition to the correlation analyses, paired t-tests will be performed to 
compare the actual values of each ECHO/MRI measurement to each other at 
each time point.   Finally, Bland-Altman plots will be generated at baseline, 
follow-up and using the change in measure for each of the MRI/ECHO derived 
measures. 
13.3 Power and Sample Size 
Assuming a sample size of 32 evaluable patients (assuming a drop rate of up to 
20% by 3-months) we will need to enroll 40 total patients.  With n=32 patients, we 
have 80% power to detect a 0.511 standard deviation difference using a paired t-
test assuming alpha=0.05 (2-sided).  If the drop-out rate is lower (i.e., n=40) then 
the detectable difference would be 0.45 standard deviations. This difference 
should demonstrate a meaningful change in the cardiotoxic parameters of 
interest.  In addition, with n=32 patients we can estimate the 3-month cardio-
toxicity rate within +/- 0.181 using an 95% Exact Clopper-Pearson 2-sided 
confidence interval. 
13.4 Estimated Accrual Rate 
We expect to accrue at least 30  patients per year. 
13.5 Estimated Study Length 
Assuming a sample size of 40, we expect to accrue 30 patients per year and 
complete the study in <2 years. 

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References 
1. American Cancer Society: Cancer Facts and Figures 2015 Atlanta, GA: American Cancer
Society, 2015.
2. NCCN Guidelines: Acute Myeloid Leukemia Version 1.2015: National Comprehensive Cancer
Network, 2015.
3. Schiller NB, Skiôldebrand CG, Schiller EJ, et al. Canine left ventricular mass estimation by
two-dimensional echocardiography. Circulation. 1983;68: 210-216.
4. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man.
Anatomic validation of the method. Circulation. 1977;55: 613-618.
5. Wahr DW, Wang YS, Schiller NB. Left ventricular volumes determined by two-dimensional
echocardiography in a normal adult population. Journal of the American College of Cardiology.
1983;1: 863-868.
6. Asanoi H, Kameyama T, Ishizaka S, Miyagi K, Sasayama S. Ventriculoarterial coupling
during exercise in normal human subjects. International Journal of Cardiology. 1992;36: 177-
186.
7. Kim RJ, Wu E, Rafael A, et al. The Use of Contrast-Enhanced Magnetic Resonance Imaging
to Identify Reversible Myocardial Dysfunction. New England Journal of Medicine. 2000;343:
1445-1453.
8. Natori S, Lai S, Finn JP, et al. Cardiovascular Function in Multi-Ethnic Study of
Atherosclerosis: Normal Values by Age, Sex, and Ethnicity. American Journal of
Roentgenology. 2006;186: S357-S365.
9. Hortobagyi GN, Yap HY, Kau SW, et al. A comparative study of doxorubicin and epirubicin in
patients with metastatic breast cancer. Am J Clin Oncol. 1989;12: 57-62.
10. Shapira J, Gotfried M, Lishner M, Ravid M. Reduced cardiotoxicity of doxorubicin by a 6-
hour infusion regimen. A prospective randomized evaluation. Cancer. 1990;65: 870-873.
11. Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and
dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest
Oncology Group study. J Natl Cancer Inst. 1991;83: 926-932.
12. Chauncey TR, Gundacker H, Shadman M, et al. Sequential phase II Southwest Oncology
Group studies (S0112 and S0301) of daunorubicin and cytarabine by continuous infusion,
without and with ciclosporin, in older patients with previously untreated acute myeloid
leukaemia. Br J Haematol. 2010;148: 48-58.
13. Mewton N, Opdahl A, Choi E-Y, et al. Left Ventricular Global Function Index By Magnetic
Resonance Imaging- A Novel Marker for Assessment of Cardiac Performance for the Prediction
Of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis. Hypertension. 2013;61:
770-778.
14. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International
Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and
Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21:
4642-4649.

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Appendix A – Protocol Registration Form 
DEMOGRAPHICS 
Patient: Last Name: _____________________ First Name: ___________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
SEX:   
  Male      Female 
Ethnicity (choose one):   Hispanic 
Non-Hispanic
Race (choose all that 
apply): 
 WHITE           BLACK            ASIAN 
 PACIFIC ISLANDER                 NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2  
Primary Diagnosis: ____________________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
ECOG Performance Status: ___ ___ ___ 
Protocol Registrar can be contact by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – 
Friday. 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-mailed to 
the registrar at 336-7136772 or registra@wakehealth.edu.
PROTOCOL INFORMATION 
Date of Registration: 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________  
Date protocol treatment started: 
___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to registration) 
YES  NO
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
PID # (to be assigned by ORIS): 
___ ___ ___ ___ ___ ___ ___ ___ 

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Appendix B – Subject Eligibility Checklist 
IRB Protocol No. 
WFBCCC Protocol No. 22616 
Study Title: Cytarabine plus Continuous Infusion Daunorubicin Induction Therapy for Adults 
with Acute Myeloid Leukemia; A Feasibility Study with Cardiac MRI Monitoring 
Principal Investigator:  Bayard Powell, MD 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to 
Confirm * 
(Please document 
dates and lab results) 
Patients must have morphologically confirmed 
newly diagnosed acute myelogenous leukemia 
(AML) with blood or bone marrow disease. Patients 
with only extramedullary disease in the absence of 
bone marrow or blood involvement are eligible. 
Note: This protocol uses WHO diagnostic criteria for 
AML. Patients with acute promyelocytic leukemia 
(APL, FAB, M3) or blastic transformation of chronic 
myelogenous leukemia (CML) are not eligible. 
□ 
□ 
≥ 18 years of age. 
□ 
□ 
ECOG performance status 0-3. 
□ 
□ 
Patients with ECHO EF ≥ 45% within 28 days prior 
to registration. 
□ 
□ 
Women of child-bearing potential and men must 
agree to use adequate contraception (hormonal or 
barrier method of birth control; abstinence) prior to 
study entry and for the duration of study 
participation. Should a woman become pregnant or 
suspect she is pregnant while participating in this 
study, she should inform her treating physician 
immediately. 
□ 
□ 
Women of child-bearing potential and men must 
agree to use adequate contraception (hormonal or 
barrier method of birth control; abstinence) prior to 
study entry and for the duration of study 
participation. 
□ 
□ 
Ability to understand and willingness to sign an 
informed IRB-approved informed consent document 
□
□ 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        26 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria is 
present 
Source Used to 
Confirm * 
(Please document 
dates and lab results) 
Patients who have received prior induction 
chemotherapy for AML or MDS. Temporary prior 
measures such as apheresis or hydroxyurea are 
allowed. Patients who have received a limited and 
short-term exposure of ATRA (all trans retinoic acid) 
while AML-M3 (Acute Promyelocytic Leukemia) was 
being ruled out, and which has been discontinued, 
will be eligible. 
□ 
□ 
Patients receiving any other investigational agents. 
□ 
□ 
Patients with prolonged QTc interval (> 500 msec) 
determined by EKG within 28 days prior to 
registration. 
□ 
□ 
Patients not suitable for cardiac MRI. 
Contraindications include:  
•
Intracranial metal, pacemakers, defibrillators,
functioning neurostimulator devices, or other
implanted electronic devices;
•
Ferromagnetic cerebral aneurysm clips, or other
intraorbital/intracranial metal;
•
Allergy to Gadolinium or other severe drug
allergies;
•
Claustrophobia;
•
Congestive heart failure (NYHA class III or IV);
•
Significant valvular disease, or significant
pulmonary disease requiring supplemental
oxygen therapy
□ 
□ 
History of allergic reactions attributed to compounds 
of similar chemical or biologic composition to 
daunorubicin or cytarabine. 
□ 
□ 
Patients with documented CNS involvement. 
□ 
□ 
Patients who are known to be HIV+ may be eligible 
providing they meet all of the following additional 
criteria within 28 days prior to registration: 
• CD4 cells ≥ 500/mm3
• Viral load of < 50 copies HIV mRNA/mm3 if on
cART or < 25,000 copies HIV mRNA if not on cART
• No zidovudine or stavudine as part of cART
Patients who are HIV+ and do not meet all of these
criteria are not eligible for this study.
□ 
□ 
Patients with other uncontrolled intercurrent illness 
or psychiatric illness/social situations that would 
limit compliance with study requirements. 
□
□ 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        27 
Pregnant women are excluded from this study 
because of the potential for teratogenic or 
abortifacient effects with drugs used in this study. 
Because there is an unknown but potential risk for 
adverse events in nursing infants secondary to 
treatment of the mother with the drugs used in this 
study, breastfeeding should be discontinued prior 
to beginning treatment. 
□ 
□ 
This subject is      
 eligible / 
ineligible     for participation in this study. 
ORIS Assigned PID: __________________ 
Signature of research professional confirming eligibility:_______________________ Date: 
_______________ 
Signature of Treating Physician**:  _____________________________________ Date: 
_______________ 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing
the source, specifically state which document in the medical record was used to assess eligibility. Also
include the date on the document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14”
**Principal Investigator signature can be obtained following registration if needed

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        28 
Appendix C – Mandatory STRC SAE Reporting Guidelines 
Safety and Toxicity Review Committee (STRC; 
previously known as CROC)  Serious Adverse 
Event (SAE) Notification SOP 
    Date: 11/17/2016 
Mandatory STRC SAE Reporting Requirements 
This document describes STRC reporting and use of the electronic submission form that is submitted for 
unexpected grade 4 and any grade 5 (death during protocol intervention) SAEs on CCCWFU 
Institutional interventional trial patients. There are multiple entities that require reporting of SAEs. 
Each entity has different rules for what is reported, and how it is reported.  
Rules used by other entities (Institutional Review Board (IRB), AdEERS, MedWatch, etc.) should NOT be 
used to evaluate whether an event should be reported to STRC. Only the rules for reporting described in 
this document should be considered. 
As defined in the NCI Data Table 4 reporting guidelines, CCCWFU Institutional Interventional studies 
covered by these reporting requirements are defined as: In-house, internally reviewed trials, including 
those collaborative studies conducted with industry sponsorship in which the center is a primary 
contributor to the design, implementation, and monitoring of the trial, or participation in a multi-site 
trial initiated by an institutional investigator at another center.  Institutional trials are almost always 
authored by a researcher here at CCCWFU. Institutional protocols are labeled NCI Code=”I” for 
Institutional on the protocol screen in ORIS. Cooperative group protocols are not considered 
Institutional, but Research Base trials are classified as Institutional. 
The STRC is responsible for reviewing SAEs for CCCWFU Institutional Interventional studies, as defined 
above. STRC currently requires that unexpected grade 4 and all grade 5 SAEs on these trials be reported 
to the STRC for review. All Clinical Protocol and Data Management (CPDM) staff members assisting a PI 
in documenting and reporting an SAE that qualifies for STRC reporting are responsible for informing a 
clinical member of the STRC by phone (or in-person), followed by informing the entire committee via the 
required email notification. 
THESE REPORTING REQUIREMENTS APPLY TO any faculty or staff member on the study team for a 
CCCWFU Institutional Interventional trial. Once an event is observed, it is the responsibility of the 
person who observed the event to be sure that it is reported. 
What is considered an SAE under this mandatory procedure? 
Any unexpected grade 4 event and all grade 5 events (death during protocol intervention) should be 
reported. These events should be reported if they occur while a patient is on study treatment or if they 
occur within 30 days of last study treatment (even if patient begins a new treatment during the 30 days). 
This window of 30 days should be the standard window to be used in all protocols unless a specific 
scientific rationale is presented to suggest that a shorter window can be used to identify events.  In 
addition, if it is not clear whether the Grade 4 is unexpected it should be reported. 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        29 
Table 1: Summary of STRC Reporting Requirements for Institutional Pilot, Phase 1, Phase 2  
and Phase 3 Interventional Trials  
STRC reporting may not be appropriate for specific expected adverse events for protocols. In those 
situations the adverse events that will not require STRC reporting must be specified in the text of the 
approved protocol. 
STRC notification responsibilities of the person handling the reporting/documenting of the SAE: 
1.
Make a phone call (or speak in person) to the appropriate clinical member of the STRC as listed
below (page if necessary)—see note 2 below
2.
Submit the STRC Notification Form WITHIN 24 HOURS of first knowledge of the event. This form is
found at either the ORIS main menu page or by going to http://ccc.wfubmc.edu/oris/strc.aspx.
This will ensure that all persons that need to be made aware of the event (i.e., study team members
and STRC members) will be notified; remember to file a copy of your confirmation. (Form
instructions will walk you through the required fields, consult the help page for further instructions.)
3.
Ensure that you document that the appropriate person(s) on the STRC has been contacted.  This
documentation is placed on the STRC Notification form described above.
4.
Follow up with/update the clinical member(s) of STRC regarding any new developments or
information obtained during the course of the SAE investigation and reporting process.
Elements to complete the electronic STRC form: 
Please use ‘reply to All’ when responding with one of these terms:  Definite, Probable, Possible, 
Unlikely, or Unrelated 
1.
Patient ID (ORIS PID)
2.
Patient Name
3.
Patient MR#
ADVERSE EVENT 
Grade 1, Grade 2, Grade 3 
Grade 4 
Grade 5 
Unexpected 
Expected 
Unexpected 
Expected 
Unexpected 
Expected 
Unrelated 
Not Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT TO 
STRC 
Unlikely 
Not Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT TO 
STRC 
Possible 
Not Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT TO 
STRC 
Probable 
Not Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT TO 
STRC 
Definite 
Not Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT TO 
STRC 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        30 
4.
CCCWFU(ORIS) Study Number
5.
Title
6.
PI Name
7.
PI Contact Number
8.
PI Comments
9.
STRC Clinician notified by Phone
10. Notified Date
11. Notified Time
12. STRC Clinician Comments
13. Category [This is the Grade – Either Unexpected Grade 4 or Grade 5 should be entered]
14. Additional Information (IRB Reporting)(after discussion with PI or STRC Clinician
i.
Is This Event Related to Protocol Treatment?
ii.
Is Suspension of the Protocol Needed?
iii.
Any Changes to Consent or Protocol Needed?
iv.
Was Nature or Severity of Event Unexpected?
15. Date of the event.
16. Brief description (include brief clinical history relevant to this event, including therapies believed
related to event).
17. Date of Last Dose before event
18. Relevant tests/labs.
19. Other Relevant Treatment Information
20. Other Comments/Notes (include regimen of chemo and dates the patient received them if
known).
21. Cc (email) (include treating Physician; separate email list with comma”,”)
22. Your Name
23. Your Email
24. Confirm Your Email
The Clinical Members of STRC to Notify by Phone or Page: 
Bayard Powell, MD – Director-at-Large, CCCWFU; Section Head, Hematology/Oncology 
Glenn Lesser, MD – Hematology Oncology 
Stefan Grant, MD, JD-Hematology Oncology 
 Jimmy Ruiz, MD-Hematology Oncology 
Kathryn Greven, MD – Vice Chair – Radiation Oncology
Marissa Howard-McNatt, MD – General Surgery 
Mercedes Porosnicu, MD- Hematology Oncology 
Definition of Unavailable:  
As a general guideline if the first clinician that is contacted does not respond to the phone call or page 
within a reasonable amount of time, then initiate contact with their backup.  Give the back-up a 
reasonable amount of time to respond to a phone call or page before contacting another member. This 
is a general guideline.  You must use your best judgment as a clinical research professional given the 
time of day, severity of the SAE, and other circumstances as to when it is appropriate to contact backup 
clinicians.  If the event occurs near the end of day, then leave messages (voice or email) as appropriate 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        31 
and proceed with submitting your STRC notification form.  The important criteria is that you have taken 
reasonable steps to notify and document that you have initiated some type of contact to one or more of 
the clinical members of STRC. 
STRC CLINICAN RESPONSIBILITY: 
It is the responsibility of the STRC clinician to review all reported events, evaluate the events as they are 
reported; and communicate a response to the Investigator, event reporter and the members of STRC. 
The review will include but not be limited to the information reported; there may be times when 
additional information is needed in order for an assessment to be made and further communication 
directly with the investigator may be warranted. STRC reserves the right to agree with the investigator’s 
assessment if STRC does not agree with the investigator. STRC reserves the right to suspend the trial 
pending further investigation. 
Is there any immediate danger or harm that could be present for a future patient based on the 
information provided in the STRC report – and if so an immediate suspension of enrollment should take 
place. 
AMENDMENTS TO PREVIOUS REPORTS 
If you are not able to supply all pertinent information with the initial submission, once the additional 
information is available do not submit a new report. Go to the original email that was received by STRC 
and others “reply to all” and entitle your email “Amendment for (list date of event and patient ID) this 
will avoid duplications of the same event. List the additional information which you are reporting. 
Acronyms and Definitions 
STRC-Safety and Toxicity Review Committee 
SAE-Serious Adverse Event 
IRB-Institutional Review Board 
CCCWFU-Comprehensive Cancer Center Wake Forest University 
ORIS-Oncology Research Information System 
NCI-National Cancer Institute 
CPDM-Clinical Protocol and Data Management 
Interventional Trials-Therapeutic Level 1 and Level 2 trials 
Therapeutic Level 1-A cancer treatment protocol aimed at directly treating/curing the patient’s cancer. 
Therapeutic Level 2-A therapeutic protocol not cancer treatment involves clinical activity to treat 
symptoms, improve the patient’s quality of life, or preven 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        32 
Appendix D - Response Criteria14 
Date: ___ ___ / ___ ___ / ___ ___ 
Allogeneic stem cell transplant received? 
 Yes 
 No 
Date: __ __/__ __/__ __ 
Please check the response that applies to this patient: 
 Morphologic leukemia-free state 
 Complete Remission (CR) 
Complete Remission with Incomplete Recovery (CRi) 
Cytogenetic Complete Response (CRc) 
Molecular Complete Response (CRm) 
Partial Remission (PR)  
Treatment Failures 
Treatment Failure due to Resistant Disease (TFRD) 
Treatment Failure due to Complication of Aplasia (TFCA) 
Treatment Failure due to Indeterminate Cause (TFIC) 
Morphologic Relapse  
Molecular or cytogenetic relapse 
Induction Death 
Treating Physician Signature: ________________________  Date: ___ ___ / ___ ___ / ___ ___ 
PI Signature: ____________________________  
  Date: ___ ___ / ___ ___ / ___ ___ 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        33 
Appendix E: Cardiac Function Worksheet 
Cardiac Function Worksheet 
PID_______________________ 
Study Number________________ 
MRN________________________ 
Continuous infusion completed? 
Y / N#  
#If No, Amount infused: ______ml 
Duration: _____hrs _____min 
Baseline (Pre-
Induction) 
Date: 
___/___/___ 
*Prior to
Induction Cycle 
2 
Date: 
___/___/___ 
3 mo. follow-up 
or relapse 
3 Mo.___ 
Follow-up___ 
Date: 
___/___/___ 
6 mo. follow-up or relapse 
6 Mo.___ 
Follow-up___ 
Date: ___/___/___ 
MRI 
w/o contrast 
NA 
w/o contrast 
w/o contrast 
EF % 
LVEDV ml 
LVESV ml 
Mean T1 
Mean T2 
Global longitudinal strain % 
 MRI Completed 
Y / N 
NA 
Y / N 
Y / N 
Person recording information 
ECHO 
Full 3D 
Ltd w/ strain 
Ltd w/ strain 
NA 
EF % 
LVEDV ml 
LVESV ml 
Global longitudinal strain % 
ESV ml 
Mitral inflow E velocity 
Mitral inflow A velocity 
  Mitral inflow A’ velocity 
Mitral inflow E’ velocity 
ECHO Completed 
Y / N 
Y / N 
Y / N 
NA 
Person recording information 
Troponin Levels 
Pre-Induction 
Cycle 1/ Day 4 
*Cycle 2/ Day 3
Notes 
Levels 
ng/ml 
ng/ml 
ng/ml 
Brand of troponin assay used# 
Person recording information 
#    1 = TnI-Ultra Assay, Siemens (Centaur)     2 = Access 2 AccuTnI+3 Assay Beckman Coulter 
Definitions 
MRI = Magnetic Resonance Imaging 
ESV = End systolic volume 
ECHO = Echocardiogram 
ml = milliliters 
EF = Ejection Fraction 
LVESV = left ventricular end systolic volume 

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC 
MRI MONITORING, INDUCTION THERAPY FOR ADULTS WITH ACUTE MYELOID 
LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        34 
LVEDV = left ventricular end diastolic volume 
* only for those requiring a second cycle of induction
Ltd w/ strain = Limited with strain measures 
w/o contrast = without contrast 
INSTRUCTIONS FOR COMPLETING THE CARDIAC FUNCTION WORKSHEET 
Purpose: This purpose of this form is to record data related to cardiac function as derived from the two 
of the main study tasks; magnetic resonance imaging (MRI) and echocardiogram (ECHO). 
1.
Record the patient information in the appropriate spaces (name, study number, MRN).
2.
Transfer data regarding infusion completion.
3.
At each time point, fill in the date.
4.
Before performing each task note the specification for the procedure within each time point
(grayed row).
5.
Record the data for each task.
6.
At the end of the data collection for each task (MRI or ECHO), circle “Y” or “N” to indicate
whether the patient was able to complete the study task.
7.
For the individual recording the data, please sign or initial at the bottom of the data collection
form in the “Person recording information” line in either the MRI or ECHO section .
8.
For the troponin levels, enter the brand of assay being used with either a 1 or 2 using the key
designated by #
a.
Enter the levels once obtained  in ng/ml
9.
Those entering data please sign the designated section “person recording information” in the
Troponin levels section

CYTARABINE PLUS CONTINUOUS INFUSION DAUNORUBICIN, WITH CARDIAC MRI MONITORING, INDUCTION 
THERAPY FOR ADULTS WITH ACUTE MYELOID LEUKEMIA; A FEASIBILITY STUDY 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) CCCWFU 22616 
Protocol version date: 06/022017 
        35 
Appendix F – Adverse Event Log 
WFBCCC Adverse Event (AE) Log 
PI: _________________ 
PID: _________________ 
MRN: ________________ 
Cycle Start Date: _____________ 
Cycle End Date: _______________ 
Cycle #: __________ 
Adverse Event 
CTC Term 
Value 
(-5 if non-
numeric) 
Grade 
(0-5) 
per CTC 
Start 
Date 
Attribution 
1=Related 
2=Probably 
3=Possible 
4=Unlikely 
5=Unrelated 
Treating MD 
Initials/Date 
End 
Date 
Expected 
1=Yes  
0=No 
*Serious
Adverse
Event (SAE)  
1=Yes 0=No 
Dose 
Limiting 
Toxicity 
(DLT) 
1=Yes 
0=No 
Action 
Taken 
1=None   
2=Tx 
withheld 
3=Tx D/C 
4=Tx 
adjusted 
5=Other 
Reportable?  
1=IRB 
2=STRC 
3=FDA 
4=Sponsor 
*Serious Adverse Event: Hospitalization; Disability; Birth Defect; Life-threatening; Death.
CTCAE Version 4- http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE 4.03 2010-06-14 QuickReference 8.5x11.pdf