Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia
Phase: NA
Conditions: Acute Undifferentiated Leukemia, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Mast Cell Leukemia, Myeloid/NK-cell Acute Leukemia, Untreated Adult Acute Lymphoblastic Leukemia, Untreated Adult Acute Myeloid Leukemia
Sponsor: Wake Forest University Health Sciences

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 1 of 22 
 
Principal Investigator: 
 
Timothy S Pardee, M.D., Ph.D. 
Section on Hematology and Oncology 
Wake Forest University School of Medicine 
Medical Center Blvd. 
Winston-Salem, NC 27157 
 
Co-Investigators: 
 
Heidi D. Klepin, M.D., M.S. 
Section on Hematology and Oncology 
Wake Forest University School of Medicine 
Medical Center Blvd. 
Winston-Salem, NC 27157 
 
 
Bayard Powell, M.D. 
Section Head, Hematology and Oncology 
Wake Forest University School of Medicine 
Medical Center Blvd. 
Winston-Salem, NC 27157 
 
 
Susan Lyerly, P.A.-C. 
Section on Hematology and Oncology 
Wake Forest University School of Medicine 
Medical Center Blvd. 
Winston-Salem, NC 27157 
 
 
Megan Manuel, N.P. 
Section on Hematology and Oncology 
Wake Forest University School of Medicine 
Medical Center Blvd. 
Winston-Salem, NC 27157 
 
 
Sarah Dralle, N.P. 
Section on Hematology and Oncology 
Wake Forest University School of Medicine 
Medical Center Blvd. 
Winston-Salem, NC 27157 
 
 
Biostatistician: 
 
Scott Isom, M.S. 
Comprehensive Cancer Center 
Wake Forest University School of Medicine 
Medical Center Blvd. 
Winston-Salem, NC 27157 
 
 
NCT01869777 
 
Protocol Version Date 07.25.14 
 
 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 2 of 22 
 
1.0   
Background and Rationale 
 
The acute leukemias in adults are characterized by resistance and poor outcomes. Acute 
myeloid leukemia (AML) and acute lymphoid leukemia (ALL) are aggressive malignancies that 
lead to the accumulation of immature myeloid or lymphoid precursors, resulting in progressive 
marrow failure and death 1. They affect approximately 19,000 people per year in the United 
States; despite decades of research, the overall 5-year survival remains a disappointing 30-40% 
2-4. The current treatment is intensive induction chemotherapy followed by consolidation using 
chemotherapy or a stem cell transplant 2,5.   
 
Selecting patients for intensive therapy is a major challenge in the acute leukemias. 
There are multiple prognostic factors in the acute leukemias that are used to try and select the 
best candidates for intensive induction therapy. The most powerful single prognostic factor in 
the acute leukemias is cytogenetics. Using standard karyotyping techniques patients can be 
divided into 3 prognostic categories; good, intermediate and poor. They are characterized by 5 
year overall survival rates of 55%, 24% and 5% respectively 6. Age is also a powerful prognostic 
factor in the acute leukemias. For patients over 60 with acute leukemia, the prognosis is grave 
(five-year survival of less than 10%) 7-9. These patients have many co-morbidities and increased 
resistant disease 2,5. Both acute leukemias in adulthood disproportionately affect the elderly 
(median age of onset of 72 and >60 for AML and ALL, respectively) 4,10.  The presence of poor-
risk cytogenetic factors is increased in elderly patients as well as expression of multi-drug efflux 
pumps 11-12. Performance status is another important prognostic factor and the ability to tolerate 
induction therapy decreases as performance status worsens regardless of age 8. For older 
patients with poor performance status it is currently acceptable clinical practice to offer only 
supportive care. In AML this has led some authors to conclude that standard induction 
chemotherapy should not be offered to elderly patients13. In contrast other groups have found a 
positive clinical impact of standard therapy in older AML patients with increased survival and 
less time in hospital than those offered only supportive care14. In order to better help clinicians 
decide what patients should be offered intensive therapy a number of prognostic scoring 
systems have been developed15. The majority of these systems rely heavily on the cytogenetics 
of the leukemia and this information is generally not available at the time of diagnosis. An 
additional prognostic factor that could be easily obtained at the time of diagnosis would a major 
step forward. In addition to deciding on what initial therapy to give an AML patient there is 
another major clinical decision point. A nadir marrow is obtained on day 14 following standard 
induction therapy and if there is significant residual disease a second course of induction is 
usually attempted. In many cases patients have experienced significant complications by day 14 
making additional chemotherapy difficult to safely administer. There are very few studies on 
what prognostic factors are important when considering a second course of induction therapy. 
This is further complicated by the lack of rigorously performed studies to establish the predictive 
power of a positive nadir marrow. An additional prognostic factor that could be easily obtained 
on day 14 would be of significant help to clinicians.  
 
Bioimpedance phase angle is prognostic in multiple disease states. Phase angle is 
measured by bioimpedance and reflects cell membrane integrity, nutritional status and muscle 
mass16. It has been found to be prognostic in a number of conditions such as end stage renal 
disease, HIV and COPD17-19. Additionally, it is prognostic in multiple tumor types including 
pancreatic, colorectal, breast and head and neck. In a recent report it was found to be strongly 
prognostic for patients with hematologic malignancies undergoing allogeneic stem cell 
transplants20. Standardized phase angle measurements are made non-invasively, can be done 
quickly and reproducibly and with no patient discomfort. Measurements are taken by placing 2 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 3 of 22 
 
electrodes on the hand and 2 on the foot from the same side of the patient. A small voltage is 
applied between the electrodes and the timing of induced the current is measured. The current 
is approximately 1000 times lower than the sensitivity of sensory neurons and thus cannot be 
felt by the patient and has no known biological effect. This study seeks to establish the 
feasibility and prognostic power of standardized phase angle in acute leukemia patients 
undergoing intensive induction chemotherapy.   
 
2.0  
Objectives 
 
2.1 To determine the feasibility of obtaining standardized phase angle measurements on 
patients hospitalized for treatment of newly diagnosed acute leukemia. 
 
2.2 To evaluate the association between standardized phase angle measured at the 
start of therapy and treatment-related outcomes including: 
Primary outcome: Treatment related mortality (defined as 60-day mortality)  
Secondary outcomes: Evaluate the association of the day 14 standardized phase angle 
and treatment related outcomes, 30-day mortality, length of hospitalization, transfer to 
intensive care unit during induction, treatment response (14 day bone marrow response, 
complete remission), receipt of post-remission therapy, overall survival. 
 
2.3 An exploratory analysis investigating associations with the primary and secondary 
outcomes using different ways to categorize the baseline standardized phase angle 
measurement (obtained on the first day of treatment) and, for AML patients, the 
standardized phase angle measure obtained just prior to the nadir marrow. 
 
3.0   
Patient Selection Criteria 
 
 
3.1  Eligible 
 
 
 
3.11   Hospitalized for newly diagnosed acute leukemia 
 
 
3.12 
Receiving induction treatment while hospitalized  
 
 
3.13 
Willing and able to provide written informed consent 
 
 
3.2 Ineligible 
 
 
 
 
 
3.21 
Presence of a pacemaker or defibrillator. 
 
 
3.22 
Patients pregnant at the time of enrollment.  
3.23 
Any condition or abnormality which may, in the opinion of the investigator, 
compromise the safety of patients. 
3.24 
Unable/unwilling to follow protocol requirements 
 
 
4.0  
Study Design 
Eligible patients with newly diagnosed acute leukemia will have phase angle 
measurements recorded within the first 3 days of treatment. AML patients will have a 
second phase angle measurement taken within 2 days of the nadir marrow. Whenever 
possible, measurements will be taken prior to any invasive procedures (bone marrow 
biopsy, leukophoresis, PICC line placement, etc.). In addition data on pertinent 
covariates including age, demographic data, tumor biology, white blood cell count, LDH, 
need of total parental nutrition or placement of a feeding tube and comorbid conditions 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 4 of 22 
 
will be collected. There will be no intervention done as a result of the phase angle 
measurement. Patients will be followed at routine visits per standard of care for two 
years or until death. 
 
5.0 
Data Management 
All data will be de-identified and stored in a password protected REDCap database in 
accordance with HIPAA. Research Electronic Data Capture (REDCap) software is a 
secure, web-based application designed to support survey creation, survey 
administration and data capture for research studies.  Records to be kept on each 
subject will include only the data specified in Appendices B, C, D, E and F. Only study 
personnel will have access to the data. 
 
6.0     Registration  
Eligible patients must be registered with the CCCWFU Registrar. Following registration, 
patients should have a baseline phase angle measurement taken. If a patient does not 
agree to have the measurement following registration, the patient’s registration on the 
study may be canceled. The Registrar should be notified of cancellations as soon as 
possible. 
 
To register a patient, the following documents should be completed by the research 
nurse or data manager and faxed (336-713-6772) to the Registrar: 
• 
Signed patient consent form/HIPAA authorization form 
• 
On-Study/Registration Form (Appendix A) 
 
The research nurse or data manager will then call (336-713-6767) the Registrar between 
the hours of 0800-1600 EST Monday-Friday to verify eligibility.  To complete the 
registration process, the Registrar will: 
• 
assign a patient study number 
• 
register the patient on the study 
 
7.0 
Statistical Considerations 
 
Description of measures 
 
Standardized phase angle 
Standardized phase angle will be calculated as in 20 (standardized phase angle = 
(measured phase angle−phase angle ref)/SD ref). Reference values and standard 
deviation come from measurements of phase angle in over 200,000  healthy German 
adults21.  
 
Mortality 
30 day mortality rate is defined as the percent of patients no longer alive at 30 days after 
registration. In the rare case that a patient is lost to follow up before 30 days, the patient 
will be treated as missing. 
 
60 day mortality rate is defined as the percent of patients no longer alive at 60 days after 
registration. Patients that are discharged to hospice care before 60 days without a 
known date of death will be counted towards 60 day mortality. In the rare case that a 
patient is lost to follow up before 60 days, the patient will be treated as missing. 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 5 of 22 
 
Treatment response 
14 day bone marrow response is defined as hypoplastic marrow with less than 20% 
cellularity and 5% blasts. 
 
Complete remission is defined as less than 5% marrow blasts, absolute neutrophil count 
>1000, platelet count >100,000 and freedom from red cell transfusions. 
 
Feasibility Analysis 
If the study fails to accrue 20 patients during the first year of accrual it will be deemed 
unlikely to meet its ultimate accrual goal and the study will be terminated.  
 
Primary analysis 
This study’s primary endpoint is the association between standardized phase angle and 
60 day mortality. Standardized phase angle will be treated as a continuous measure for 
the primary analysis. Since we will be using a standardized measure of phase angle, for 
power calculations we will assume a standard deviation of one and investigate the 
effects of a one unit change. A sample size of 102 patients would give us 80% power to 
detect an odds ratio of 2.1, using a logistic regression model with a 0.05 significance 
level and a 60 day mortality rate of 20%. With an expected accrual rate of 50 patients 
per year, the study should complete accrual in approximately two years and complete 
follow-up (two year follow-up) four years after the first patient is enrolled.  Descriptive 
statistics will be used for baseline characteristics.  Important baseline characteristics, 
such as age, will be added to the regression model as covariates for additional analysis. 
 
Secondary analysis 
We will use logistic regression to analyze the association between standardized phase 
angle and the secondary outcomes of 30 day mortality, transfer to the intensive care 
unit, 14 day marrow response, complete remission and receipt of post-remission 
therapy. The association with overall survival will be evaluated using a Cox proportional 
hazards model. We will use a linear model to look at the association with length of 
hospital stay. It is likely that the length of hospital stay will not be normally distributed 
and will need a transformation to satisfy the normality assumption of the linear model. 
Feasibility will be analyzed qualitatively. 
 
Exploratory analysis 
We will explore other versions of the standardized phase angle measure and how they 
relate to the primary and secondary outcomes. We will evaluate using categorical cut 
points of the baseline measure and the standardized phase angle measure captured just 
prior to the nadir marrow (for AML patients). 
 
8.0 
Protection of Human Subjects 
Prior to implementation of this study, the protocol will be approved by the WFU 
Institutional Review Board (IRB). All subjects will provide written informed consent prior 
to enrollment in the study. 
 
9.0 
Data Submission Schedule 
 
Appendix A – Eligibility Checklist and Registration Form: 
 
- 
Submitted to Registrar at the time of registration 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 6 of 22 
 
Appendix B – Demographics, Social and Medical History, Baseline Lab Data Collection Form: 
 
- completed at study entry 
 
 
 
Appendix C – Comorbidity Data Collection Forms: 
 
- completed at the time of initial phase angle measurement 
 
-submitted within one week of completion 
 
Appendix D – Phase Angle Measurement Form: 
 
- completed each time a phase angle measurement is made (i.e. 1st day of treatment, 
 
prior to nadir marrow [AML patients only], and prior to any invasive procedures) 
 
-submitted within one week of completion 
 
Appendix E – Bone Marrow Biopsy and Treatment Data Collection Form: 
 
-completed as appropriate 
 
-submitted within one week of completion 
 
Appendix F – Follow-up Data Collection Form 
 
- completed as appropriate 
 
-submitted within one week of completion  
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 7 of 22 
 
10.0   References 
 
1. 
Licht JD, Sternberg DW. The molecular pathology of acute myeloid leukemia. 
Hematology Am Soc Hematol Educ Program. 2005:137-142. Prepublished on 2005/11/24 as 
DOI 2005/1/137 [pii] 
10.1182/asheducation-2005.1.137. 
2. 
Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid 
leukemia in adults: recommendations from an international expert panel, on behalf of the 
European LeukemiaNet. Blood. 2010;115(3):453-474. Prepublished on 2009/11/03 as DOI 
blood-2009-07-235358 [pii] 
10.1182/blood-2009-07-235358. 
3. 
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: The impact of 
eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 
2011;61(4):212-236. Prepublished on 2011/06/21 as DOI caac.20121 [pii] 
10.3322/caac.20121. 
4. 
Marks DI. Treating the "older" adult with acute lymphoblastic leukemia. Hematology Am 
Soc Hematol Educ Program. 2010;2010:13-20. Prepublished on 2011/01/18 as DOI 2010/1/13 
[pii] 
10.1182/asheducation-2010.1.13. 
5. 
Larson RA. Treatment of older patients with acute lymphoblastic leukemia. Annals of 
Hematology. 2006;85:79-81. 
6. 
Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are 
predictive of induction success, cumulative incidence of relapse, and overall survival in adult 
patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B 
(CALGB 8461). Blood. 2002;100(13):4325-4336. Prepublished on 2002/10/24 as DOI 
10.1182/blood-2002-03-0772 
2002-03-0772 [pii]. 
7. 
Rollig C, Thiede C, Gramatzki M, et al. A novel prognostic model in elderly patients 
with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. 
Blood. 2010;116(6):971-978. Prepublished on 2010/05/06 as DOI blood-2010-01-267302 [pii] 
10.1182/blood-2010-01-267302. 
8. 
Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 
2006;107(9):3481-3485. Prepublished on 2006/02/04 as DOI 2005-09-3724 [pii] 
10.1182/blood-2005-09-3724. 
9. 
Brenner H, Pulte D, Gondos A. Improvement in survival in younger patients with acute 
lymphoblastic leukemia from the 1980s to the early 21st century. Blood. 2009;113(7):1408-1411. 
10.1182/blood-2008-06-164863. 
10. 
Juliusson G, Antunovic P, Derolf A, et al. Age and acute myeloid leukemia: real world 
data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 
2009;113(18):4179-4187. Prepublished on 2008/11/15 as DOI blood-2008-07-172007 [pii] 
10.1182/blood-2008-07-172007. 
11. 
Kuendgen A, Germing U. Emerging treatment strategies for acute myeloid leukemia 
(AML) in the elderly. Cancer Treat Rev. 2009;35(2):97-120. Prepublished on 2008/10/28 as DOI 
S0305-7372(08)00284-3 [pii] 
10.1016/j.ctrv.2008.09.001. 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
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12. 
Larson RA. Acute lymphoblastic leukemia: older patients and newer drugs. Hematology 
Am Soc Hematol Educ Program. 2005:131-136. Prepublished on 2005/11/24 as DOI 2005/1/131 
[pii] 
10.1182/asheducation-2005.1.131. 
13. 
Kantarjian H, Ravandi F, O'Brien S, et al. Intensive chemotherapy does not benefit most 
older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010. Prepublished on 
2010/07/30 as DOI blood-2010-03-276485 [pii] 
10.1182/blood-2010-03-276485. 
14. 
Juliusson G. Older patients with acute myeloid leukemia benefit from intensive 
chemotherapy: an update from the Swedish Acute Leukemia Registry. Clin Lymphoma Myeloma 
Leuk. 2011;11 Suppl 1:S54-59. Prepublished on 2011/11/09 as DOI S2152-2650(11)00027-9 
[pii] 
10.1016/j.clml.2011.02.003. 
15. 
Wheatley K, Brookes CL, Howman AJ, et al. Prognostic factor analysis of the survival of 
elderly patients with AML in the MRC AML11 and LRF AML14 trials. Br J Haematol. 
2009;145(5):598-605. Prepublished on 2009/04/07 as DOI BJH7663 [pii] 
10.1111/j.1365-2141.2009.07663.x. 
16. 
Kyle UG, Bosaeus I, De Lorenzo AD, et al. Bioelectrical impedance analysis--part I: 
review of principles and methods. Clin Nutr. 2004;23(5):1226-1243. Prepublished on 2004/09/24 
as DOI 10.1016/j.clnu.2004.06.004 
S0261561404000937 [pii]. 
17. 
Faisy C, Rabbat A, Kouchakji B, Laaban JP. Bioelectrical impedance analysis in 
estimating nutritional status and outcome of patients with chronic obstructive pulmonary disease 
and acute respiratory failure. Intensive Care Med. 2000;26(5):518-525. Prepublished on 
2000/08/03 as DOI. 
18. 
Oliveira CM, Kubrusly M, Mota RS, Silva CA, Choukroun G, Oliveira VN. The phase 
angle and mass body cell as markers of nutritional status in hemodialysis patients. J Ren Nutr. 
2010;20(5):314-320. Prepublished on 2010/03/23 as DOI S1051-2276(10)00009-9 [pii] 
10.1053/j.jrn.2010.01.008. 
19. 
Shah S, Whalen C, Kotler DP, et al. Severity of human immunodeficiency virus infection 
is associated with decreased phase angle, fat mass and body cell mass in adults with pulmonary 
tuberculosis infection in Uganda. J Nutr. 2001;131(11):2843-2847. Prepublished on 2001/11/06 
as DOI. 
20. 
Urbain P, Birlinger J, Ihorst G, Biesalski HK, Finke J, Bertz H. Body mass index and 
bioelectrical impedance phase angle as potentially modifiable nutritional markers are 
independent risk factors for outcome in allogeneic hematopoietic cell transplantation. Ann 
Hematol. 2013;92(1):111-119. Prepublished on 2012/09/13 as DOI 10.1007/s00277-012-1573-4. 
21. 
Bosy-Westphal A, Danielzik S, Dorhofer RP, Later W, Wiese S, Muller MJ. Phase angle 
from bioelectrical impedance analysis: population reference values by age, sex, and body mass 
index. JPEN J Parenter Enteral Nutr. 2006;30(4):309-316. Prepublished on 2006/06/29 as DOI 
30/4/309 [pii]. 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
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Appendix A - Eligibility and Source Document Checklists, 
Registration Form 
 
CCCWFU # 99113 
 
REGISTRATION GUIDELINES 
 
The following guidelines have been developed in order to ensure timely registration of 
your patient. 
 
All patients entered on any CCCWFU trial, whether treatment, companion, or cancer 
control trial, must be registered with the CCCWFU Protocol Registrar or entered into 
ORIS Screening Log within 24 hours of Informed Consent.  Patients must be registered 
prior to the initiation of treatment.   
 
In order to ensure prompt registration of your patient, please: 
1. Complete the Eligibility Checklist (attached) 
2. Complete the Protocol Registration Form (attached) 
3. Alert the WFUHS 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. Please 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, please provide a printout of 
the results.  Please ensure that the most recent lab values are sent. 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 10 of 22 
 
CCCWFU # 99113  
 
Eligibility Checklist                                         Page 1      
                                                                                        
Yes No N/A Inclusion Criteria (All responses must be YES in order to enter 
study) 
Eligibility 
Confirmation 
(registrar) 
 
 
 
1. Is the patient hospitalized for newly diagnosed acute 
leukemia? 
 
 
 
 
2. Is the patient receiving induction treatment while 
hospitalized? 
 
 
 
 
3. Is the patient willing and able to provide written informed 
consent? 
 
Yes No N/A Exclusion Criteria (All responses must be NO in order to enter 
study) 
 
 
 
 
1. Does the patient have a pacemaker or defibrillator? 
 
 
 
 
2. Is the patient pregnant? 
 
 
 
 
3. Does the patient have any abnormality which may, in the 
opinion of the investigator, compromise the safety of 
patients? 
 
 
 
 
4. Is the patient unable or unwilling to follow protocol 
requirements? 
 
 
 
 
 
 
 
 
Signature: ________________________________ Date: _________________ 
Please send source documentation with Eligibility Form.  
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 11 of 22 
 
CCCWFU # 99113  
 
 Protocol Registration Form                          Page 2 
 
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) 
Zip Code:  ___ ___ ___ ___ ___ 
 
Primary Diagnosis: _____________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
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) : 
______________________       
Informed written consent (consent must be signed prior to registration): 
 YES 
  NO 
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by ORIS): 
___ ___ ___ ___ ___ ___ ___ ___ 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 12 of 22 
 
CCCWFU # 99113    Eligibility Source Documentation Checklist              Page 3 
(to be submitted with Protocol Registration Form) 
Source Documents Needed 
 or 
N/A 
1 
Documentation that patient is hospitalized for newly diagnosed acute 
leukemia 
 
2 
Documentation that patient is receiving induction treatment while 
hospitalized 
 
3 
Signed informed consent document 
 
4 
Documentation that patient is not pregnant 
 
5 
Documentation that patient is free from any condition or abnormality which 
may, in the opinion of the investigator, compromise the safety of patients 
 
 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance 
Phase Angle in Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 13 of 22 
 
Appendix B:  Social and Medical History, Baseline Lab Data Collection Form (Page 1 of 2) 
 
Demographics 
Social History: 
 
Married:   
 
Yes ___ 
No ___ 
 
Tobacco use: 
Current _____ 
Former ______ 
Never ______ 
 
Alcohol abuse: 
Current _____ 
Former_______ 
Never ______ 
 
 
Baseline Labs on date of admission: (allow one decimal point) 
WBC  
 
 
 
___ ___.___  
 
SODIUM  
 
___ ___.___  
 
 
HEMOGLOBIN  
___ ___.___      
POTASSIUM  
___ ___.___ 
HEMATOCRIT      ___ ___.___  
 
BUN  
 
 
___ ___.___  
 
 
 
 
 
       
 
 
 
 
 
 
 
GLUCOSE 
 
___ ___.___  
 
 
 
PLATELETS        
___ ___ ___   
 
CREATININE   ___ ___.___  
 
 
NEUTROPHILS  
___ ___.___   
 
ALBUMIN 
 
___ ___ ___  
 
BANDs 
 
 
 
___ ___.___  
 
T. BILIRUBIN 
___ ___.___ 
ANC  
 
 
 
___ ___.___  
 
ALK PHOS  
__ ___.____  
 
 
 
 
 
 
 
 
 
 
 
 
AST  
 
 
___ ___.___ 
LDH  
 
___ ___.___  
ALT 
 
      ___ ___.___ 
 
GFR  
      ___ ___.___ 
 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 14 of 22 
 
Appendix B:  Demographics, Social and Medical History, Baseline Lab Data Collection Form 
(Page 2 of 2) 
 
Past Medical History 
 
Number of comorbidities:  _________ (0-20) 
 
Past History of:   
 
 
 
 
 
(per documentation in medical record at time of admission) 
 
Congestive Heart Failure  Y___ N___       
 
Depression              
Y___ N___ 
 
 
 
Coronary artery disease     Y___ N___       
 
Osteoporosis  
 
Y___ N___ 
 
Cerebrovascular Disease   Y___ N___       
 
Rheumatologic disease 
Y___ N___  
 
 
 
 
 
      
 
 
(SLE, RA, scleroderma, Sjogrens) 
(Stroke, TIA)  
 
 
 
 
 
Diabetes Mellitus 
           Y___ N___       
 
Cognitive Impairment 
Y___ N___ 
 
COPD                                 Y___ N___       
 
VTE      
 
 
Y___N___ 
(Emphysema) 
 
 
 
      
 
(Venous thrombosis, DVT, PE) 
 
Hypertension  
           Y___ N___      
 
 Cardiac valve disease 
Y___ N___ 
 
Renal Dysfunction            Y___ N___       
 
Cirrhosis 
 
 
Y___ N___ 
 
Previous Cancer 
           Y___ N___       
 
MDS (H&P only) 
 
Y___N___ 
(Excludes non-melanoma skin) 
 
 
 
 
 
      
 
 
MDS (path report only) 
Y___N___ 
If yes, then cancer type ________________________ 
 
Prior treatment with: (check) Chemotherapy ___ Radiation  ___   Surgery     ___ 
 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 15 of 22 
 
Appendix C:  Comorbidity Data Collection Forms (Page 1 of 3) 
 
Charlson Comorbidity Index 
 
Comorbidity and score (circle) 
 
Myocardial infarction 
 
 
 
 
 
 
 
1 
 
 
Congestive heart failure  
 
 
 
 
 
 
1 
 
 
Cerebrovascular disease  
 
 
 
 
 
 
1 
 
 
Peptic ulcer  
 
 
 
 
 
 
 
 
1 
 
 
Hepatic ulcer (mild) 
 
 
 
 
 
 
 
1 
 
 
Diabetes (mild/moderate)  
 
 
 
 
 
 
1 
 
 
Pulmonary disease (mild/moderate) 
 
 
 
 
 
1 
  
 
Diabetes (with severe end stage organ damage) 
 
 
 
2 
 
Renal disease (moderate or severe) 
 
 
 
 
 
2 
 
Hepatic disease (moderate or severe)  
 
 
 
 
3 
 
Solid tumor with metastases 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total Score____________ 
 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 16 of 22 
 
Appendix C:  Comorbidity Data Collection Forms (Page 2 of 3) 
 
Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) 
Comorbidity and score (circle) 
 
 
Cardiac 
 
 
 
 
 
 
 
 
 
1 
(CAD, CHF, MI, EF ≤ 50%) 
 
Arrhythmia  
 
 
 
 
 
 
 
 
1 
(Atrial fibrillation or flutter,  
sick sinus or ventricular arrhythmia) 
 
Cerebrovascular disease  
 
 
 
 
 
 
1 
(TIA or CVA) 
 
Peptic ulcer  
 
 
 
 
 
 
 
 
2 
(Requiring treatment) 
 
Hepatic Disease (mild) 
 
 
 
 
 
 
 
1 
(Chronic hepatitis, bilirubin>ULN to  
1.5 X the ULN,or AST/ALT>ULN to  
2.5 X the ULN) 
 
Diabetes 
 
 
 
 
 
 
 
 
 
1 
(Requiring treatment with medication) 
 
Pulmonary (moderate) 
 
 
 
 
 
 
 
2 
(DLCO and/or FEVI 66-80% 
or dyspnea with slight activity) 
 
Rheumatologic 
 
 
 
 
 
 
 
 
2 
(SLE, RA, polymyositis, mixed CTD,  
or polymyalgia rheumatica) 
 
Inflammatory bowel disease 
 
 
 
 
 
 
1 
(Crohns disease or ulcerative colitis) 
 
Renal (moderate/severe)  
 
 
 
 
 
 
2 
(Serum creatinine>2mg/dL,  
mixed CTD, or prior renal transplant) 
 
Prior solid tumor   
 
 
 
 
 
 
 
3 
(Treated at any point in patient’s history,  
excluding non-melanoma) 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 17 of 22 
 
Appendix C:  Comorbidity Data Collection Forms (Page 3 of 3) 
 
Hepatic (moderate/severe) 
 
 
 
 
 
 
3 
(Liver cirrhosis, bilirubin>1.5 X the ULN,  
or AST/ALT>2.5 X the ULN) 
 
Obesity 
 
 
 
 
 
 
 
 
 
1 
(Body mass index > 35 kg/m²) 
 
Infection 
 
 
 
 
 
 
 
 
 
1 
(Requiring use of antimicrobial treatment) 
 
Psychiatric Disturbance  
 
 
 
 
 
 
1 
(Depression or anxiety requiring  
psychiatric consult or treatment) 
 
Heart Valve Disease 
 
 
 
 
 
 
 
3 
(Except mitral valve prolapse) 
 
Severe pulmonary  
 
 
 
 
 
 
 
3 
(DLCO and or FEVI ≤ 65% or dyspnea at rest or requiring oxygen) 
 
 
 
 
 
 
 
 
 
Total score: _______________ 
 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 18 of 22 
 
Appendix D – Phase Angle Measurement Form 
 
To be completed with each phase angle measurement: 
 
ORIS Assigned PID:  ___ ___ ___ ___ ___ ___ ___ ___ 
 
Physical Exam: 
 
Date of Exam: ___ ___ / ___ ___ / ___ ___ 
 
Weight:  ____ (kg) 
 
Height:  ____  (cm) 
 
Systolic Blood Pressure (SBP):  _____ (50-250) 
 
Diastolic Blood Pressure (DBP): _____ (30-130) 
 
Pulse:  _____ (30-180) 
 
Phase Angle: _______    R:_________  Xc________ 
 
 
For AML Patients: Second Phase Angle Measurement taken just prior to the nadir marrow: 
 
Physical Exam: 
 
Date of Exam: ___ ___ / ___ ___ / ___ ___ 
 
Weight:  ____ (kg) 
 
Height:  ____  (cm) 
 
Systolic Blood Pressure (SBP):  _____ (50-250) 
 
Diastolic Blood Pressure (DBP): _____ (30-130) 
 
Pulse:  _____ (30-180) 
 
Phase Angle: _______    R:_________  Xc________ 
 
 
 
 
 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 19 of 22 
 
Appendix E – Bone Marrow Biopsy and Treatment Data Collection Forms 
 
BONE MARROW BIOPSY: 
 
DATE ______/______/_______ 
 
Diagnosis: AML or ALL _________ 
 
Blast %: _______________________ 
 
CYTOGENETICS: _________________________________________(free text) 
 
 
 
RISK GROUP:  FAVORABLE ___ INTERMEDIATE ___ UNFAVORABLE ____ 
 
APL:  YES___ NO___   
 
 
Hypoplastic marrow cellularity %:  __________________________ 
 
TREATMENT: 
 
HOSPITALIZED FOR INDUCTION CHEMOTHERAPY: Y___  N___ 
 
DATE OF ADMISSION: _________________________________________________ 
 
DATE OF DISCHARGE: ________________________________________________ 
 
DATE INDUCTION CHEMOTHERAPY INITIATED:  
______________________ 
 
TYPE OF CHEMOTHERAPY ADMINISTERED (check one):  
 
1.  ___ AraC+anthracycline+etoposide (7+3+3) 
2.  ___ AraC+ anthracycline (7+3) 
3.  ___As per CALGB 10102 
4.  ___other _________________________________________(document regimen) 
 
 
NUMBER OF CYCLES OF CHEMOTHERAPY: _____________(range 0-5) 
 
RESIDUAL DISEASE ON 14-DAY BONE MARROW BIOPSY:  Y___    N____  N/A____ 
 
REQUIRED ICU DURING HOSPITAL STAY:   Y___ 
N___ 
 
DEATH WITHIN 30 DAYS OF INITIAL TREATMENT:  Y ___ N___ 
 
DEATH WITHIN 60 DAYS OF INITIAL TREATMENT:  Y ___ N___ 
 
DISPOSITION:  HOME ____ SNF ____ ALF ____ HOSPICE ___ DECEASED ____ 
 
Need for total parenteral nutrition or feeding tube placement during induction hospitalization:   
Y____  N____  

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 20 of 22 
 
Appendix F -FOLLOW-UP (POST INDUCTION HOSPITALIZATION) Data Collection Form  
(page 1 of 2) 
 
ACHIEVED COMPLETE REMISSION: Y____ N____ 
Comment for Complete Remission: ________________________________(free text, 200 characters) 
RECEIVED POST-REMISSION THERAPY:  Y____  N____ 
Number of cycles of consolidation therapy: _____ (0-5) 
Complete consolidation information below as applicable: 
Date of 1st consolidation: ________ 
Specify type of 1st consolidation: hypomethylating agent (5-azacitidine/decitabine) ___  
 
 
 
 
autologous transplantation___  
 
 
 
 
reduced intensity allogeneic transplant___  
 
 
 
 
full allogeneic transplant ___ 
 
 
 
 
Ara-C ____ 
 
 
 
 
If received Ara-C for 1st consolidation, record dose:  
 
 
 
 
 
3gm/m2__ 2 gm/m2__1.5 g/m2__1gm/m2__ 500mg/m2___ 
 
 
 
 
Other___ 
 
 
 
 
If other record type: ______________________________ 
 
 
 
 
 
 
 
 
(text, 50 characters) 
Date of 2nd consolidation: ________ 
Specify type of 2nd consolidation: hypomethylating agent (decitabine/azacitidine) ___  
 
 
 
 
autologous transplantation___  
 
 
 
 
reduced intensity allogeneic transplant___  
 
 
 
 
full allogeneic transplant ___ 
 
 
 
 
Ara-C ____ 
 
 
 
 
If received Ara-C for 2nd consolidation, record dose:   
 
 
 
 
3gm/m2__ 2 gm/m2__1.5 g/m2__1gm/m2__ 500mg/m2___ 
 
 
 
 
Other___ 
 
 
 
 
If other record type: ______________________________ 
 
 
 
 
 
 
 
 
(text, 50 characters) 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 21 of 22 
 
Appendix F -FOLLOW-UP (POST INDUCTION HOSPITALIZATION) Data Collection Form  
(page 2 of 2) 
 
Date of 3rd consolidation: ________ 
Specify type of 3rd consolidation: hypomethylating agent (decitabine/azacitidine) ___  
 
 
 
 
autologous transplantation___  
 
 
 
 
reduced intensity allogeneic transplant___  
 
 
 
 
full allogeneic transplant ___ 
 
 
 
 
Ara-C ____ 
 
 
 
 
If received Ara-C for 3rd consolidation, record dose:  
 
 
 
 
 
3gm/m2__ 2 gm/m2__1.5 g/m2__1gm/m2__ 500mg/m2___ 
 
 
 
 
Other___ 
 
 
 
 
If other record type: ______________________________ 
 
 
 
 
 
 
 
 
(text, 50 characters) 
 
RECEIVED BONE MARROW TRANSPLANTATION: Y____ N____ 
 
IF YES, SPECIFY TYPE:  (PICK ONE) 
REDUCED INTENSITY ____ 
 
 
 
 
 
 
 
 
 
 
 
 
FULL ALLOGENEIC       ____ 
 
 
 
 
 
 
 
 
 
 
 
 
AUTOLOGOUS  
    ____ 
 
SPECIFY REGIMEN: _______________________________________ (FREE TEXT, 100 characters) 
 
Date of bone marrow transplant: _________ 
 
 

Comprehensive Cancer Center of Wake Forest University 
CCCWFU #99113 – Investigating the Prognostic Importance of Bioelectrical Impedance Phase Angle in 
Adults Treated for Newly Diagnosed Acute Leukemia 
 
 
Page 22 of 22 
 
 
 
Appendix G – Survival Data 
 
 
ORIS Assigned PID:  ___ ___ ___ ___ ___ ___ ___ ___ 
 
 
Visit Date: ____ / ____ / _____ 
 
Visit Interval:   
_____ 3 Mos Post     _____ 6 Mos Post   _____ 9 Mos Post    _____  12 Mos Post 
_____ 15 Mos Post    _____ 18 Mos Post   _____ 21 Mos Post     _____ 24 Mos Post    
 _____ Other Mos Post     _____ Number of Months Post Discharge 
 
 
DATE OF LAST CONTACT: ____ / ____ / _____ 
DECEASED:  Y____ N____ 
DATE OF DEATH: ____ / ____ / _____