Impact of Cleansing With Chlorhexidine Gluconate (CHG) on Reducing Central Line Associated Bloodstream Infection (CLABSI) and Acquisition of Multi-drug Resistant Organisms (MDRO) in Children With Cancer or Those Receiving Allogeneic Hematopoietic Cell Transplantation (HCT)
Phase: PHASE3
Conditions: Bacterial Infection, Benign Neoplasm, Malignant Neoplasm, Methicillin-Resistant Staphylococcus Aureus Infection, Myeloid Neoplasm, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia
Sponsor: Children's Oncology Group

ACCL1034 
CHILDREN’S ONCOLOGY GROUP 
ACCL1034 
Impact of Cleansing with Chlorhexidine Gluconate (CHG) on Reducing Central Line Associated 
Bloodstream Infection (CLABSI) and Acquisition of Multi-drug Resistant Organisms (MDRO) in 
Children with Cancer or Those Receiving Allogeneic Hematopoietic Cell Transplantation (HCT) 
A Groupwide Study (Limited to US and Canada sites) 
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, AND SHOULD NOT BE COPIED, REDISTRIBUTED OR USED FOR ANY OTHER
PURPOSE. MEDICAL AND SCIENTIFIC INFORMATION CONTAINED WITHIN THIS PROTOCOL IS NOT INCLUDED TO AUTHORIZE OR
FACILITATE THE PRACTICE OF MEDICINE BY ANY PERSON OR ENTITY. RESEARCH MEANS A SYSTEMATIC INVESTIGATION,
INCLUDING RESEARCH DEVELOPMENT, TESTING AND EVALUATION, DESIGNED TO DEVELOP OR CONTRIBUTE TO GENERALIZABLE
KNOWLEDGE. THIS PROTOCOL IS THE RESEARCH PLAN DEVELOPED BY THE CHILDREN’S ONCOLOGY GROUP TO INVESTIGATE A
PARTICULAR STUDY QUESTION OR SET OF STUDY QUESTIONS AND SHOULD NOT BE USED TO DIRECT THE PRACTICE OF MEDICINE 
BY ANY PERSON OR TO PROVIDE INDIVIDUALIZED MEDICAL CARE, TREATMENT, OR ADVICE TO ANY PATIENT OR STUDY SUBJECT.
THE PROCEDURES IN THIS PROTOCOL ARE INTENDED ONLY FOR USE BY CLINICAL ONCOLOGISTS IN CAREFULLY STRUCTURED 
SETTINGS, AND MAY NOT PROVE TO BE MORE EFFECTIVE THAN STANDARD TREATMENT. ANY PERSON WHO REQUIRES MEDICAL
CARE IS URGED TO CONSULT WITH HIS OR HER PERSONAL PHYSICIAN OR TREATING PHYSICIAN OR VISIT THE NEAREST LOCAL HOSPITAL 
OR HEALTHCARE INSTITUTION. 
 
  
 
 
 
 
Version Date: 
09/24/2014 
Activated:    11/04/2013 
Closed:        04/21/2017
Amendment: 
#3a 
Version Date: 09/24/2014 
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ACCL1034 
TABLE OF CONTENTS 
 
SECTION 
PAGE 
STUDY COMMITTEE 
4 
ABSTRACT 
6 
EXPERIMENTAL DESIGN SCHEMA 
7 
1.0 
GOALS AND OBJECTIVES (SCIENTIFIC AIMS) 
8 
1.1 
Primary 
8 
1.2 
Secondary 
8 
2.0 
BACKGROUND 
8 
2.1 
Overview and Significance of the Problem and Rationale for Selected Outcomes 
8 
2.2 
Rationale for Selection of CHG Cleansing 
9 
3.0 
STUDY ENROLLMENT PROCEDURES AND PATIENT ELIGIBILITY 
12 
3.1 
Study Enrollment 
12 
3.2 
Patient Eligibility Criteria 
15 
4.0 
TREATMENT PLAN 
17 
4.1 
Overview of Treatment Plan 
17 
4.2 
Concomitant Therapy Restrictions 
18 
4.3 
Schedule for CHG/Control Cleansing 
19 
5.0 
DOSE MODIFICATIONS FOR TOXICITIES 
21 
5.1 
Skin Breakdown 
21 
5.2 
Emergency Un-Blinding 
21 
6.0 
AGENT INFORMATION 
21 
6.1 
Source and Pharmacology 
21 
6.2 
Toxicity 
21 
6.3 
Formulation and Stability 
22 
6.4 
Guidelines for Administration 
22 
6.5 
Supplier 
22 
7.0 
EVALUATIONS/MATERIAL AND DATA TO BE ACCESSIONED 
22 
7.1 
Required Clinical, Laboratory and Disease Evaluations 
23 
7.2 
Optional Study 
27 
8.0 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY 
CRITERIA 
27 
8.1 
Criteria for Removal from Protocol Therapy 
27 
8.2 
Off Study Criteria 
27 
9.0 
STATISTICAL CONSIDERATIONS 
28 
9.1 
Statistical Design 
28 
9.2 
Patient Accrual and Expected Duration of Trial 
28 
9.3 
Statistical Analysis Methods 
28 
9.4 
Gender and Minority Accrual Estimates 
32 
10.0 
EVALUATION CRITERIA 
33 
10.1 
Common Terminology Criteria for Adverse Events (CTCAE) 
33 
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ACCL1034 
11.0 
ADVERSE EVENT REPORTING REQUIREMENTS 
33 
11.1 
Purpose 
33 
11.2 
Determination of Reporting Requirements 
33 
11.3 
Reporting of Adverse Events for Commercial Agents - via CTEP-AERS 
33 
11.4 
Routine Adverse Event Reporting 
34 
12.0 
RECORDS AND REPORTING 
35 
12.1 
CDUS 
35 
13.0 
CENTRAL LINE ASSOCIATED BLOODSTREAM INFECTION (CLABSI) AND 
COLLECTION OF LEFT OVER CLINICAL BLOOD CULTURE ISOLATES 
35 
13.1 
CDC Criteria for Central Line Associated Bloodstream Infection (CLABSI). To be used 
by the investigators coding CLABSI 
35 
13.2 
Positive clinical blood culture isolates 
36 
14.0 
MDRO DATA COLLECTION 
37 
14.1 
Any cultures with the targeted organisms listed in Appendix III will be evaluated as 
potential MDRO. 
37 
15.0 
SPECIMEN REQUIREMENTS 
38 
15.1 
Screening Swabs 
38 
APPENDIX I: DEFINITIONS FOR THE INTENSITY OF A HEMATOPOIETIC STEM CELL 
TRANSPLANT CONDITIONING REGIMEN 
41 
APPENDIX II: STANDARDIZED INSTRUCTIONS FOR USE OF STUDY CLEANSING 
CLOTHS 
42 
APPENDIX III: TARGETED ORGANISMS 
43 
APPENDIX IV: CTEP REGISTRATION PROCEDURES 
44 
APPENDIX V: YOUTH INFORMATION SHEETS 
46 
REFERENCES 
50 
SAMPLE INFORMED CONSENT / PARENTAL PERMISSION FOR PARTICIPATION IN 
RESEARCH 
53 
 
 
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ACCL1034 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AGENT NSC# AND IND# 
 
Chlorhexidine gluconate (CHG) 
 
 
 
 
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ACCL1034 
 
The Children's Oncology Group has received a Certificate of Confidentiality from the federal government, 
which will help us protect the privacy of our research subjects. The Certificate protects against the 
involuntary release of information about your subjects collected during the course of our covered studies. 
The researchers involved in the studies cannot be forced to disclose the identity or any information collected 
in the study in any legal proceedings at the federal, state, or local level, regardless of whether they are 
criminal, administrative, or legislative proceedings. However, the subject or the researcher may choose to 
voluntarily disclose the protected information under certain circumstances. For example, if the subject or 
his/her guardian requests the release of information in writing, the Certificate does not protect against that 
voluntary disclosure. Furthermore, federal agencies may review our records under limited circumstances, 
such as a DHHS request for information for an audit or program evaluation or an FDA request under the 
Food, Drug and Cosmetics Act. The Certificate of Confidentiality will not protect against mandatory 
disclosure by the researchers of information on suspected child abuse, reportable communicable diseases, 
and/or possible threat of harm to self or others. 
 
 
ABSTRACT 
Reducing the frequency of healthcare-associated infections (HAI) is a national healthcare priority. Central 
line associated bloodstream infections (CLABSI) and infections due to multidrug resistant organisms 
(MDRO) are two of the most prevalent and serious HAI experienced by patients with cancer. Chlorhexidine 
gluconate (CHG) is more effective than other antiseptics in lowering cutaneous microbial levels and daily 
bathing or cleansing the skin with CHG has been shown to reduce CLABSI and MDRO acquisition in 
critically ill adults. This study is a randomized, double-blinded, controlled trial to evaluate the efficacy of 
CHG cleansing in preventing CLABSI and MDRO acquisition in children with cancer or those receiving 
allogeneic hematopoietic cell transplantation (HCT). Eligible patients include those between 2 months and 
21 years of age with an eligible central venous catheter which is planned to be in place for at least 3 month; 
the reason for the catheter can be a planned allogeneic transplant, or an oncology diagnosis requiring 
chemotherapy for > 3 months or an oncology diagnosis requiring < 3 months of chemotherapy followed by 
transplantation (allogeneic or stem cell rescue) during the study period. A total of 450 subjects will be 
randomized to CHG or control cleansing up to 10 days before to 7 days after starting a cycle of 
chemotherapy or conditioning. Subjects will receive study cleansing daily, beginning after randomization 
and continuing for 90 days. Skin swabs will be collected in order to track CHG and antimicrobial resistance 
in skin microorganisms. Bacterial isolates from any positive blood cultures will also be collected. The 
primary outcome will be the occurrence of CLABSI. Secondary outcomes include any bloodstream 
infection, acquisition of MDRO, and CHG and antimicrobial resistance in skin and bloodstream 
microorganisms. 
 
 
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ACCL1034 
EXPERIMENTAL DESIGN SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACCL1034 Enrollment 
Allogeneic hematopoietic cell transplantation (HCT) patient undergoing 
transplant procedure, or a non-transplant patient with cancer receiving 
> 3 months chemotherapy or receiving < 3 month of chemotherapy 
followed by HCT with an eligible central venous catheter (CVC)  that is 
planned to be in place for at least 3 months.
Control Cleansing 
CHG Cleansing 
Randomization  
to Chlorhexidine 
Gluconate (CHG) 
Cleansing or Control 
Cleansing 
•
Baseline data collection and baseline swabs (ship within 24 
hours); 
•
Daily cleansing  for 90 days; 
•
Daily monitoring for skin reactions; 
•
Daily cleansing diary; and 
•
Monitor for positive blood cultures for 90 days. 
Day 90: End of Cleansing 
•
Obtain 3rd set of swabs (ship within 24 hours); 
•
Day 90 product count; and  
•
Complete the satisfaction questionnaire. 
Evaluations 
•
Clinical care (section 7.1.2); 
•
Positive cultures for MDRO (section 7.1.3); and 
•
Bathing compliance (section 7.1.6). 
End of Study 
Day 45  
•
Obtain 2nd set of swabs (ship within 24 hours); and 
•
Day 45 product count. 
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ACCL1034 
 
1.0 
GOALS AND OBJECTIVES (SCIENTIFIC AIMS) 
1.1 
Primary 
To determine whether chlorhexidine gluconate (CHG) cleansing decreases central line 
associated bloodstream infection (CLABSI) in children with cancer or those receiving an 
allogeneic hematopoietic cell transplantation (HCT). 
1.2 
Secondary 
1.2.1 
To determine whether CHG cleansing decreases acquisition of multi-drug resistant 
organisms [MDRO: vancomycin resistant enterococci (VRE), methicillin resistant 
Staphylococcus aureus (MRSA), etc.] in children with cancer or those receiving 
allogeneic HCT. 
1.2.2 
To determine whether CHG cleansing in children with cancer or those receiving 
allogeneic HCT is associated with cutaneous bacterial isolates with reduced 
susceptibility to CHG. 
1.2.3 
To determine whether CHG cleansing decreases positive blood cultures in children 
with cancer or those receiving allogeneic HCT. 
 
 
2.0 
BACKGROUND 
2.1 
Overview and Significance of the Problem and Rationale for Selected Outcomes 
Reducing the frequency of healthcare-associated infections is a national healthcare 
priority.1 Central line associated bloodstream infections (CLABSI) and infections due to 
epidemiologically important multidrug resistant organisms (MDRO) are two of the most 
prevalent and serious healthcare associated infections experienced by patients with cancer.  
 
CLABSI is the single most common healthcare-associated infection in patients with cancer 
and carries the highest attributable morbidity and mortality.2,3 Up to 25-50% of HCT 
recipients will experience a bloodstream infection in the first year after transplantation.2,3 
Approximately 50% of these occur in the pre-engraftment period, where attributable 
mortality is estimated to be 12.5%.2 As a result, patients with a pre-engraftment 
bloodstream infection have a one-year post-transplant survival rate of 46.8% versus 64.1% 
in those without.2 High bloodstream infection rates are not restricted to patients receiving 
transplantation. In a phase 3 pediatric acute myeloid leukemia trial (Children’s Cancer 
Group 2891), 39-58% of patients experienced a bacterial infection during induction 
chemotherapy and fatal infections occurred in 1-5%, depending on the intensity of the 
chemotherapy.  
 
Evidence-based best practices aimed at reducing CLABSI are well documented in the 
literature, including hand hygiene, maximal barrier precautions, CHG skin antisepsis, 
optimal catheter site selection, and daily review of line necessity.4 Unfortunately, despite 
the evidence and application of these interventions, rates of hospital-associated 
bloodstream infection remain unacceptably high. Additional measures are required to 
further reduce CLABSI, especially in high-risk populations. 
 
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ACCL1034 
Epidemiologically important MDRO include methicillin resistant Staphylococcus aureus 
(MRSA), vancomycin resistant Enterococcus (VRE), extended spectrum beta-lactamase 
(ESBL)-producing Enterobacteriaceae, and multi-drug resistant Pseudomonas aeruginosa 
and Acinetobacter baumannii.  Immunocompromised patients are especially vulnerable to 
MDRO infections and high rates of morbidity and mortality have been documented for a 
number of the organisms including multi-drug resistant Pseudomonas,5 ESBL-producing 
Enterobacteriaceae,6 and VRE.7,8 VRE is the most common and best-studied MDRO in 
immunocompromised populations. VRE outbreaks and high-level endemic infection are 
well-documented in adult and pediatric oncology settings.9,10  In a study of adult allogeneic 
HCT recipients, VRE colonization was detected in 40% of patients; 75% of these were 
identified on the first surveillance stool culture and the remaining 25% were identified on 
subsequent cultures.8 A VRE bloodstream infection developed in 34% of colonized 
patients by day 35 post-transplantation, compared to 1.8% without VRE colonization 
(p<0.01). Despite appropriate treatment, a VRE bloodstream infection was associated with 
microbiological failure (28% of cases) and high mortality. Mortality was judged to be 
directly attributable to the VRE in 2 of the 14 patients, and in an additional 3 patients, VRE 
was judged to contribute to mortality. Another study of allogeneic transplant recipients 
found that VRE bloodstream infection developed in 12 (4.3%) of 281 patients with 
unknown colonization status.  All 12 patients with VRE bloodstream infection died within 
73 days despite appropriate therapy.  
 
Guidelines for control of MDRO have been published.11,12 However, despite 
implementation of such practices, most centers continue to have patients that acquire these 
organisms. Additional effective interventions are needed to reduce the frequency of these 
infections. 
 
2.2 
Rationale for Selection of CHG Cleansing 
CHG is an antiseptic bactericidal to Gram-positive and Gram-negative bacteria, including 
MDROs. The mechanism of action involves bacterial membrane disruption; the onset of 
action is relatively rapid and the effect is persistent. CHG is commercially available in oral 
rinses, skin and hand cleansers, surgical scrubs, and skin preps. CHG 2% impregnated 
cloths have been shown to significantly reduce bacterial levels on the skin for at least 6 
hours after application.13 Longer post-application durations have not been studied. 
However, 2% CHG in a formulation with 70% isopropyl alcohol (ChloraPrep, Cardinal 
Health, Inc.) has been shown to have activity for up to 48 hours on the skin14 and CHG is 
the component presumed to provide the persistent effect. CHG requires several 
applications to attain maximum antimicrobial benefit and repeated applications are often 
recommended.15 CHG has repeatedly been shown to be more effective than other 
antiseptics (i.e. povidone-iodine and triclocarban) in lowering cutaneous microbial levels, 
including when used for pre-operative bathing or cleansing.16-18 
 
CHG has also been studied as site preparation for placement of central venous catheters 
(CVC) and was shown to reduce CLABSI incidence, when compared to ethanol or 
povidone-iodine.19  
 
A 2% CHG-impregnated cloth product (Sage Products, Inc., Cary Illinois) was licensed by 
the FDA in 2005 for pre-operative skin preparation. This same product has been studied as 
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ACCL1034 
a cleansing or waterless bathing product in the adult critical care setting.20-22 A single-
center, 1-arm cross-over study comparing daily cleansing with CHG-impregnated cloths to 
cleansing with non-medicated cloths or bathing with soap and water, demonstrated that 
CHG cleansing resulted in decreased VRE levels on patients’ skin, healthcare workers’ 
hands, and environmental surfaces.22 In addition, with CHG cleansing, the incidence of 
new acquisition of VRE rectal colonization decreased from 26 colonizations per 1000 
patient-days to 9 per 1000 patient days. A subsequent 2-arm, cross-over study comparing 
daily CHG cleansing to daily bathing with soap and water bathing, demonstrated that 
patients receiving CHG were significantly less likely to acquire a CLABSI.20 More 
recently, a multicenter study of critically ill adults compared a 6-month period of routine 
bathing with soap and water with a subsequent 6-month period bathing with CHG solution, 
and evaluated for MDRO acquisition (new colonization or infection).21 CHG bathing was 
associated with a 32% decrease in MRSA acquisition and a 50% decrease in VRE 
acquisition. In addition, patients colonized with VRE had a 70% reduced risk of developing 
VRE bacteremia.21 Another study in critically ill adults demonstrated a significant decrease 
in CLABSI and blood culture contamination after implementation of cleansing with 
CHG.23 Currently, there are no published studies of the effect of CHG cleansing on 
occurrence of healthcare associated infections in children or in an oncology population. 
However, there is a multicenter study of critically ill pediatric patients that has 
demonstrated that CHG cleansing results in a reduced risk of bacteremia.24 Results from 
this study have been submitted for publication. 
 
CHG has a very favorable safety profile. One of the common concerns about CHG use is 
skin reaction. In a clinical study of CHG cleansing in critically ill adults, there were no 
serious adverse reactions related to CHG and a higher proportion of subjects had 
deterioration in skin condition during soap and water bathing than during CHG cleansing 
(18% vs. 3%; p = 0.02).22 There are currently no publications describing safety or 
tolerability of CHG bathing for longer durations (e.g. > 1 week) in the proposed pediatric 
population. However, the multicenter study of CHG cleansing in pediatric ICUs 
(referenced above) has provided reassuring preliminary data. Their data indicates that 1864 
children received CHG cleansing: 188 for > 2 weeks, 51 for > 4 weeks, and 16 for > 8 
weeks. There were no serious adverse events reported. The only reported events were skin 
rash. Overall, 63 rashes were reported: 43 in the CHG group and 20 in the control group. 
Of the 43 events in patients receiving CHG, 14 were judged to be related to CHG bathing. 
All CHG-related skin reactions were mild dermatitis including macular or maculopapular 
erythema24. In high concentrations, CHG can be toxic to the eyes and inner ear. Ocular 
damage has been reported to occur when CHG entered and remained in the eye during 
surgery and middle ear damage has been reported after direct instillation of CHG into the 
middle ear through a perforated tympanic membrane. The proposed protocol calls for 
cleansing with CHG cloths from the neck down. It is very unlikely that CHG would enter 
the eye or middle ear when delivered by this method. Finally, it is important to note that 
over-the-counter preparations of CHG include a 4% formulation (Hibiclens®), which is 
FDA-approved as a general skin cleanser, as well as the 2% CHG cloths (Sage Products, 
Inc.) proposed for the study. 
 
With any antimicrobial or antiseptic, it is important to understand the epidemiology and 
clinical relevance of resistance. In the case of CHG, what constitutes “resistance” and its 
associated clinical implications remains undefined. Higher minimum inhibitory 
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concentrations (MICs) to CHG have variably been associated with higher CHG minimum 
bactericidal concentrations (MBCs) and measures of killing activity. Whether these high 
MICs result in a reduction of the effect of CHG used at clinical concentrations is unclear. 
However, there are data suggesting that higher CHG MICs may be associated with 
resistance to commonly-used antibiotics,25-36 though it should be noted that these data are 
derived from cross-sectional and/or in vitro studies.  
 
One study of S. aureus demonstrated an association between MICs and bactericidal action 
of CHG in growth and time-kill studies,37 although another study of S. aureus was unable 
to demonstrate this association.38 A more recent study of S. aureus found that the presence 
of qacA/B was associated with higher MICs and MBCs to CHG.33,34  
 
There are also data suggesting that a potential association between CHG resistance and 
commonly used antimicrobials may extend beyond S. aureus. A recent cross-sectional 
study of 70 distinct clinical isolates of E. coli, K. pneumoniae, P. aeruginosa, A. 
baumannii, S. aureus, S. pyogenes, and E. faecalis demonstrated that among Gram-
negative organisms, there was a positive correlation between CHG MIC and MBC values 
and the MIC of all antibiotics tested.28 Similarly, for Gram-positive bacteria, there was a 
correlation between MBC values for CHG and several of the antibiotics tested. There are 
also limited data suggesting that in vitro exposure to CHG may result in CHG and antibiotic 
resistance. For instance, repeated passaging of Acinetobacter species in sub-inhibitory 
concentrations of CHG resulted in an elevation of MICs.27 Similarly, stable resistance to 
chlorhexidine diacetate was induced in Pseudomonas stutzeri strains by exposure to 
increasing concentrations of the agent.35 The chlorhexidine diacetate-resistant strains 
variably showed reduced sensitivity to certain other antiseptics (e.g., triclosan) as well as 
to certain antibiotics, but this varied by strain.35 A study involving one clinical MRSA 
isolate and one laboratory MRSA isolate demonstrated an increase in MICs to tested 
antibiotics following exposure to surface-dried CHG residues.36  
 
In a study of CHG cleansing in critically ill adults, the median CHG MIC was slightly 
higher for bloodstream isolates identified in the CHG arm compared to those in the soap-
and-water arm.20 However, this appeared to be due to the less frequent recovery of highly 
CHG-susceptible, gram-positive bacteria in the CHG arm, rather than to an increase in the 
absolute number or rate of isolates with elevated CHG MICs. In another study of CHG 
cleansing in adults, the median CHG MICs for VRE were similar across the 3 periods (soap 
and water, CHG impregnated cloths, and cloths without CHG). The highest MIC, 8μg/mL, 
was from an E. faecalis strain that was collected during the non-medicated cloth period.22 
A longitudinal study of both skin isolates and BSI breakthrough isolates obtained from 
patients exposed to CHG and controls is needed to better understand to what extent if any, 
clinical CHG exposure is associated with CHG susceptibility and susceptibility to 
commonly used antibiotics. Results from this study have the potential to lead to practice 
changes in the care of pediatric cancer patients and will likely lead to a better understanding 
of the clinical ramifications of CHG resistance. 
 
 
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3.0 
STUDY ENROLLMENT PROCEDURES AND PATIENT ELIGIBILITY 
3.1 
Study Enrollment 
3.1.1 
Patient Registration 
Prior to enrollment on this study, patients must be assigned a COG patient ID 
number. This number is obtained via the COG Registry system once authorization 
for the release of protected health information (PHI) has been obtained. The COG 
patient ID number is used to identify the patient in all future interactions with 
COG. If you have problems with the registration, please refer to the online help.  
 
In order for an institution to maintain COG membership requirements, every newly 
diagnosed patient needs to be offered participation in ACCRN07, Protocol for the 
Enrollment on the Official COG Registry, The Childhood Cancer Research Network 
(CCRN). 
 
A Biopathology Center (BPC) number will be assigned as part of the registration 
process. Each patient will be assigned only one BPC number per COG Patient ID. 
For additional information about the labeling of specimens please refer to the 
Pathology and/or Biology Guidelines in this protocol. 
 
Please see Appendix IV for detailed CTEP Registration Procedures for Investigators 
and Associates, and Cancer Trials Support Unit (CTSU) Registration Procedures 
including: how to download site registration documents; requirements for site 
registration, submission of regulatory documents and how to check your site’s 
registration status. 
 
3.1.2 
IRB Approval 
Sites must obtain IRB/REB approval for this protocol and submit IRB/REB 
approval and supporting documentation to the CTSU Regulatory Office before 
they can be approved to enroll patients. Allow 3 business days for processing. The 
submission must include a fax coversheet (or optional CTSU IRB Transmittal 
Sheet) and the IRB approval document(s). The CTSU IRB Certification Form may 
be submitted in lieu of the signed IRB approval letter. All CTSU forms can be 
located on the CTSU web page (https://www.ctsu.org). Any other regulatory 
documents needed for access to the study enrollment screens will be listed for the 
study on the CTSU Member’s Website under the RSS Tab. 
 
IRB/REB approval documents may be faxed (1-215-569-0206), E-mailed 
(CTSURegulatory@ctsu.coccg.org) or mailed to the CTSU Regulatory office. 
 
When a site has a pending patient enrollment within the next 24 hours, this is 
considered a “Time of Need” registration. For Time of Need registrations, in 
addition to marking your submissions as ‘URGENT’ and faxing the regulatory 
documents, call the CTSU Regulatory Helpdesk at: 1-866-651-CTSU. For general 
(non-regulatory) questions call the CTSU General Helpdesk at: 1-888-823-5923. 
 
 
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Study centers can check the status of their registration packets by querying the 
Regulatory Support System (RSS) site registration status page of the CTSU 
members’ web site by entering credentials at https://www.ctsu.org. For sites under 
the CIRB initiative, IRB data will automatically load to RSS. 
 
Note: Sites participating on the NCI CIRB initiative and accepting CIRB 
approval for the study are not required to submit separate IRB approval 
documentation to the CTSU Regulatory Office for initial, continuing or 
amendment review. This information will be provided to the CTSU Regulatory 
Office from the CIRB at the time the site’s Signatory Institution accepts the CIRB 
approval. The Signatory site may be contacted by the CTSU Regulatory Office or 
asked to complete information verifying the participating institutions on the study. 
Other site registration requirements (i.e., laboratory certifications, protocol-
specific training certifications, or modality credentialing) must be submitted to the 
CTSU Regulatory Office or compliance communicated per protocol instructions. 
 
3.1.3 
Study Enrollment 
Patient enrollment will be facilitated using the Oncology Patient Enrollment 
Network (OPEN). OPEN is a web-based registration system available on a 24/7 
basis. To access OPEN, the site user must have an active CTEP-IAM account 
(check at < https://eapps-ctep.nci.nih.gov/iam/index.jsp >) and a 'Registrar' role on 
either the lead protocol organization (LPO) or participating organization roster. 
 
All site staff will use OPEN to enroll patients to this study. It is integrated with the 
CTSU Enterprise System for regulatory and roster data and, upon enrollment, 
initializes the patient position in the Rave database. OPEN can be accessed at 
https://open.ctsu.org or from the OPEN tab on the CTSU members’ side of the 
website at https://www.ctsu.org.  
 
Prior to accessing OPEN, site staff should verify the following: 
 
• 
All eligibility criteria have been met within the protocol stated timeframes. 
• 
All patients have signed an appropriate consent form and HIPAA 
authorization form (if applicable). 
 
Note: The OPEN system will provide the site with a printable confirmation of 
registration and treatment information. Please print this confirmation for your 
records. 
 
Further instructional information is provided on the CTSU members' web site 
OPEN tab or within the OPEN URL (https://open.ctsu.org). For any additional 
questions 
contact 
the 
CTSU 
Help 
Desk 
at 
1-888-823-5923 
or 
ctsucontact@westat.com. 
 
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3.1.4 
Timing 
Patients must be enrolled before protocol therapy (use of study cleansing product) 
begins. Patients must be enrolled and randomized no more than 10 days before or 
7 days after day 1 of a conditioning regimen or day 1 of any chemotherapy cycle. 
Protocol therapy (use of study cleansing product) must be started within five (5) 
calendar days of the date of study enrollment.  
 
3.1.5 
Inclusion of Women and Minorities 
Both male and female children of all races and ethnic groups are eligible for this study. 
 
3.1.6 
Randomization 
Randomization will take place at the time a patient is enrolled. Patients will be 
assigned to either CHG or control cleansing product in a 1:1 ratio. Randomization 
will be stratified by myeloablative or reduced intensity allogeneic transplantation 
versus non-myeloablative allogeneic transplantation versus oncology patients 
receiving chemotherapy with or without a subsequent transplantation (see 
Appendix I for definitions). The randomization sequence will remain concealed to 
the site study team. Each site will be provided with a starter kit, containing 
identically packaged CHG and control product. Lot numbers will be used to 
differentiate between study and control product. After randomization of a subject, 
the site will be informed which lot number to use from the starter kit. Subsequently, 
patient-specific kits containing the appropriate product will be shipped by the 
coordinating site (Seattle) to the study site. Site-specific research staffs are to refer 
to the “Drug Management” document on the protocol web page.  
 
3.1.7 
Blinding  
The subject, investigators, and site-specific research and clinical staff who are 
involved with the conduct of the study will remain blinded to the treatment. Sage 
Products, Inc. will supply identically packaged CHG and control product to the 
coordinating site (Seattle). Lot numbers will be used to track CHG and control 
products. Only Sage and Seattle Children’s Investigational Drug Service will know 
what product is assigned to each lot number. The coordinating site (Seattle) will 
label each subject’s product with the subject-specific study number and ship the 
labeled product to the subject’s site.  
 
 
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3.1.8 
Accountability 
To ensure that the subject receives appropriate product, each site will maintain 
accurate records of all study products received and dispensed. The site will use the 
accountability record to document which product was given to the patient from the 
study pack. The study product will be packaged in a box which will have a two-
part tear off label. Before the box is given out to the subject, one part of the label 
will be torn off and affixed to the patient specific accountability record. This tear 
off label will, at minimum, contain information as to study product dispensed (lot 
#, date and COG patient ID #). The accountability records will be reviewed at 
regular intervals by the coordinating site (Seattle). 
 
3.2 
Patient Eligibility Criteria 
Important note: The eligibility criteria listed below are interpreted literally and cannot 
be waived (per COG policy posted 5/11/01). All clinical and laboratory data required for 
determining eligibility of a patient enrolled on this trial must be available in the patient's 
medical/research record which will serve as the source document for verification at the 
time of audit.  
 
See Section 7.1 for required studies to be obtained prior to starting protocol therapy. 
 
INCLUSION CRITERIA 
3.2.1 
Age 
Patients must be > 2 months of age and < 21 years of age at enrollment. 
 
3.2.2 
Diagnosis 
3.2.2.1 
Transplant Patients 
All patients undergoing planned allogeneic transplant (both malignant and non-
malignant diagnoses).  
 
3.2.2.2 
Oncology Patients 
• 
Patients with an oncology diagnosis that are or will be on a chemotherapy 
regimen that will last for an additional ≥ 3 months or are on or will be on 
a chemotherapy regimen for < 3 months and then proceed to transplant 
(allogeneic or autologous stem cell rescue) during the 3-month study 
period.  
 
3.2.3 
Central venous catheter 
3.2.3.1 Transplant Patients 
Patients undergoing allogeneic transplant must have, or be scheduled to have, an 
external tunneled central venous catheter (CVC) (Broviacs, Hickmans, tunneled 
percutaneously inserted central catheter (PICCs), etc.) and/or non-tunneled 
percutaneously inserted central catheter (PICC) that is expected to remain in place for 
an additional > 3 months. 
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3.2.3.2 
Oncology Patients with AML or relapsed ALL 
Patients with AML or relapsed ALL that will receive chemotherapy with/without 
transplant must have, or be scheduled to have, an external tunneled central venous 
catheter (CVC) (Broviacs, Hickmans, tunneled percutaneously inserted central 
catheter (PICCs), etc.) and/or non-tunneled percutaneously inserted central catheter 
(PICC) that is expected to remain in place for an additional > 3 months. 
 
3.2.3.3 Other Oncology Patients 
 
All other oncology patients that will receive chemotherapy with/without transplant 
must have, or be scheduled to have, an external tunneled central venous catheter 
(CVC) (Broviacs, Hickmans, tunneled percutaneously inserted catheter (PICCs), 
etc. that is expected to remain in place for an additional ≥ 3 months. 
 
EXCLUSION CRITERIA 
3.2.4 
Patients with a previous or current line infection are ineligible until 14 days after 
the completion of antibiotics. 
3.2.5 
Patients with only totally implanted CVCs (i.e. ports) are ineligible. 
3.2.6 
Patients with a known allergy or hypersensitivity to CHG are ineligible.  
3.2.7 
Patients with chronic, severe, generalized skin breakdown (such as generalized 
blistering, burns, severe graft versus host disease (GVHD) with open sores, etc.) 
are ineligible. 
3.2.8 
Patients currently enrolled on COG study ACCL0934 are not eligible until they 
have completed the infection observation period of that study. 
3.2.9 
Patients scheduled to receive broad-spectrum prophylactic antibacterial therapy 
are ineligible. Patients only receiving prophylaxis for PCP (TMP/SMX) or 
encapsulated organisms (penicillin) are eligible.  
3.2.10 Patients receiving sorafenib at the time of enrollment and those who are scheduled 
to receive sorafenib as part of a treatment plan are ineligible  
3.2.11 Patients using prophylactic antimicrobial locks in the CVC at the time of 
enrollment and those who are scheduled to receive antimicrobial locks in the CVC 
as part of a treatment plan are ineligible. 
3.2.12 Patients previously enrolled on this trial are ineligible. 
3.2.13 Females who are pregnant or breastfeeding are ineligible. 
 
 
REGULATORY  
3.2.16 All patients and/or their parents or legal guardians must sign a written informed 
consent. 
3.2.17 All institutional, FDA, and NCI requirements for human studies must be met. 
 
 
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4.0 
TREATMENT PLAN 
Timing of protocol therapy administration, response assessment studies, and surgical 
interventions are based on schedules derived from the experimental design or on established 
standards of care. Minor unavoidable departures (up to 72 hours) from protocol directed therapy 
and/or disease evaluations (and up to 1 week for surgery) for valid clinical, patient and family 
logistical, or facility, procedure and/or anesthesia scheduling issues are acceptable per COG 
administrative Policy 5.14 (except where explicitly prohibited within the protocol). 
 
4.1 
Overview of Treatment Plan 
This study is a randomized double-blind trial comparing cleansing with 2% CHG 
impregnated cloths (Sage Products, Inc.) to control cleansing with similar cloths that are 
impregnated with mild cleansers and moisturizers (Comfort Bath, Sage Products, Inc.) in 
children, adolescents, and young adults undergoing chemotherapy or conditioning for 
allogeneic HCT.  
 
At the time of enrollment and within 10 days before or 7 days after starting a cycle of 
chemotherapy or conditioning for HCT, patients will be randomized to receive either CHG 
cleansing or control cleansing (see Section 3.1.6) for 90 days. All patients and their 
healthcare providers will be blinded to the intervention. The CHG and control cleansing 
cloths will be packaged in an identical fashion to maintain blinding. 
 
Once-daily cleansing with the assigned study cloths will take place throughout the course 
of the treatment period of the study (90 days). Study cleansing will occur both while 
patients are hospitalized and when they are outpatients. Cleansing with study cloths will 
occur after, or instead of, usual bathing, and will include the whole body, except the 
face/head. Standardized instructions for cleansing with the study cloths are available on the 
protocol page on the web. Additionally, each package of study product (CHG or control) 
will include standardized cleansing instructions (See protocol webpage). 
 
4.1.1 
Tracking Compliance 
To track cleansing compliance, families will be given a daily diary formatted like 
a calendar where they will record whether study cleansing has taken place on a 
daily basis. Patients who go off protocol therapy will continue to complete daily 
diaries. Nursing diaries will also be used for inpatients. Families will also be 
contacted at day 45 and at the completion of the study and a cloth use and product 
count survey will be obtained. During the survey, families will be asked to provide 
a count of remaining product as well as provide the average number of baths 
missed since enrollment at Day 45 and since the last survey at Day 90, and provide 
the number of baths missed in the last week. Patients who go off protocol therapy 
(either prior to Day 45 or Day 90) will complete a final cloth use and product count 
survey when they are removed from protocol therapy. 
 
 
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4.1.2 
CHG-compatible soaps and lotions 
Patients receiving protocol therapy in either arm of the study can only use approved 
CHG-compatible soaps for bathing and apply approved CHG-compatible lotions 
to the body. Approved soaps and lotions will be provided to each patient for their 
use while inpatient and outpatient.  
 
4.1.3 
Non-study Daily CHG Bathing 
Patients receiving protocol therapy in either arm of the study should not use non-
study CHG products (CHG cloths or liquid soap) for daily bathing. Patients should 
only use approved CHG products as outlined in sections 4.2.1-4.2.3. 
 
4.1.4 
Subjects who develop a positive blood culture 
Subjects who develop a positive blood culture will continue the assigned study 
cleansing intervention throughout the course of the study (90 days) whether or not 
their catheter is removed. Patients who have their eligible catheter removed for any 
reason and do not have it replaced will not be followed for CLABSI beyond 2 days 
immediately following the loss of their eligible catheter, but will continue to be 
followed for MDRO, CHG resistance, and positive blood culture endpoints 
throughout the course of the study. Patients who maintain an eligible catheter will 
continue to be followed for all endpoints throughout the course of the study. 
 
4.1.5 
Subjects with treatment plan changes 
Oncology subjects who have a change in their original treatment plan will stay on 
protocol and receive study cleansing as long the central line remains in place and 
the patient continues to receive some form of chemotherapy.  
 
4.2 
Concomitant Therapy Restrictions 
4.2.1 
CVC Care (Dressing Changes and Hub Cleaning) 
Institutions may follow their standards for CVC care, which may include local 
application of CHG.  
4.2.2 
Surgical Procedures 
Institutions may continue to follow their standard processes for CHG cleansing or 
bathing prior to operative procedures (typically 1-2 uses prior to the surgical 
procedure). Institutional procedures should be followed for the care of the incision. 
4.2.3 
CHG Cleansing During ICU stay 
If the subject is admitted to the ICU, it is preferred that cleansing with the assigned 
study cloths are continued throughout the ICU stay. However, it is permissible for 
the patient to receive CHG cleansing during the ICU hospitalization only (and 
temporarily hold the assigned intervention) if this practice is standard of care at 
that institution.  
 
 
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4.2.4 
Antibiotic/Antifungal Administration  
There are no restrictions to the administration of systemic antibiotics used for 
treatment and no restrictions to the administration of anti-fungals. These data will 
be recorded on the appropriate case report forms. Study cleansing will continue 
while a patient is receiving systemic antimicrobials. 
4.2.5 
Radiation Therapy 
• 
Patients undergoing HCT, or other treatment regimens that require short 
duration (e.g. 3-4 days) radiation therapy will have study cleansing held 
on all days in which radiotherapy is administered. If indicated, patients 
will bathe with regular soap and water on the days radiation is received. 
Study cleansing product should resume if radiation therapy is interrupted 
(for example, on weekends) and re-started the day after completion of 
radiation therapy. 
• 
Patients who require long-term focal radiation therapy (such as those with 
neuroblastoma) will continue study cleansing except the focal area being 
irradiated will be avoided and bathed with regular soap and water if 
indicated. 
4.2.6 
Thiotepa therapy 
Patients receiving thiotepa will not be bathed with study product the day of and the 
day after administration of thiotepa. Institutions typically have specialized bathing 
instructions for patients receiving thiotepa. These institutional bathing protocols 
will be followed the day of and the day after receipt of thiotepa. 
4.2.7 
High-dose Cyclophosphamide 
Patients receiving high-dose cyclophosphamide (> 50 mg/kg/dose) will not be 
bathed with study product the day of and the day after administration of high-dose 
cyclophosphamide. If indicated, patients will bathe with regular soap and water the 
day of and the day after receiving high-dose cyclophosphamide.  
 
4.3 
Schedule for CHG/Control Cleansing 
Either 2% CHG or control cleansing cloths will be used daily for 90 days. Intervention and 
control cleansing products will be provided in identical packages, each containing 2 
cleansing cloths.  
 
 
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TREATMENT 
ROUTE 
DOSAGE 
DAYS 
IMPORTANT NOTES 
OBSERVATIONS 
2% CHG or 
control 
cleansing 
Topical 
skin cloths 
Cloths 
impregnated 
with 2% 
CHG or 
cloths 
impregnated 
with mild 
soap and 
moisturizers 
Once daily.  
 
Daily times 
may vary.   
 
Any missed 
doses do not 
need to be 
made up.  
Start within 5 days of 
enrollment. 
 
Use from the neck down 
only. Do not use on the head 
and face. Use regular 
“approved” soap for the face 
and wash the hair with 
shampoo. 
 
Use only once/day. If 
another bath is required, use 
regular soap and water. Use 
only soap provided or 
another “approved” soap. 
 
If a regular soap and water 
bath is desired on a routine 
basis, wash first with water 
and an approved soap.  
After the soap and water 
bath, allow the skin to dry 
and cool for several 
minutes. After the skin has 
cooled, the cloths may be 
used as directed.  
 
Do not apply lotions to the 
whole body that are not 
provided by study staff or 
are not “approved”. Any 
lotion may be applied to the 
face or hands. 
 
Do not use for preparation 
for lumbar punctures or in 
scenarios where the product 
may come in contact with 
the meninges. 
a. Baseline collection 
history, demographics 
and institutional 
standard of care.  
 
b. Collection of clinical 
care data throughout the 
treatment period.  
 
c. Monitor for cleansing 
compliance. (See 
section 7.1.6). 
 
d. Record any positive 
blood cultures during 
the study period. (See 
section 7.1.6). 
 
e. Collection of leftover 
blood isolates (See 
section 13.0). 
 
f. Record any positive 
cultures with an MDRO 
during the study 
period.(See section 
7.1.3). 
 
g. Collection of skin 
(axilla and neck) swabs 
(See sections 7.1.8 and 
14). 
 
h. Optional nares and 
perirectal swab or stool 
specimen. (See section 
7.2). 
 
For COG Supportive Care Guidelines see: 
https://members.childrensoncologygroup.org/prot/reference_materials.asp under Standard Sections for 
Protocols. See Section 5.0 for Dose Modifications based on Toxicities. For details regarding criteria for 
determining CLABSI, see Section 13.0
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5.0 
DOSE MODIFICATIONS FOR TOXICITIES 
5.1 
Skin Breakdown 
Subjects will discontinue the skin cleaning intervention and be removed from protocol 
therapy if they develop severe generalized skin breakdown (such as severe skin disruption 
from GVHD) judged by the attending physician to warrant discontinuation of the study 
cleansing intervention. Any localized wounds or areas of skin breakdown should be 
avoided while bathing.  
 
Skin Reaction 
Subjects will discontinue the skin cleaning intervention and be removed from protocol 
therapy if they develop any skin reaction thought to be caused by allergy to the cleansing 
product or any non-allergic skin reaction > Grade 3 possibly, probably, or definitely related 
to the cleansing product. 
5.2 
Emergency Un-Blinding 
If emergency un-blinding is required, the local study staff will complete an emergency un-
blinding CRF that will be forwarded to Seattle’s Investigative Drug Service. The Seattle 
Investigative drug service will contact the site investigator and provide the information. 
The Study Chair and research coordinator at the central coordinating site (Seattle) will 
remain blinded. In the event of un-blinding, the patient will be removed from protocol 
therapy (bathing cloths) but will continue to be followed for CLABSI, MDRO, CHG 
resistance, and positive blood culture endpoints. 
 
 
6.0 
AGENT INFORMATION  
Chlorhexidine Gluconate cloth, 2% 
NSC #753971 
 
 
 
 
 
 
 (04/16/12) 
6.1 
Source and Pharmacology 
Chlorhexidine gluconate is an antiseptic that exerts its bactericidal activity against Gram-
positive and Gram-negative bacteria through bacterial cell membrane disruption. The use 
of cloths impregnated with 2% chlorhexidine gluconate has demonstrated significant 
reduction of bacterial levels on the skin for at least 6 hours after application. Chlorhexidine 
gluconate requires several applications to achieve its maximum antimicrobial benefit; 
repeated applications are often recommended. Chlorhexidine gluconate has been shown to 
be more effective than other commonly used antiseptics (eg, povidone-iodine) in lowering 
cutaneous microbial levels. 
6.2 
Toxicity 
Toxicities of chlorhexidine gluconate cloths may include the following (frequency and 
timing unknown) 
 
• 
Allergic reaction 
• 
Edema – face 
• 
Nasal congestion 
• 
Dyspnea 
• 
Dry skin 
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• 
Skin and subcutaneous tissue disorders - Other, [skin redness] 
• 
Skin and subcutaneous tissue disorders - Other, [skin roughness] 
• 
Skin and subcutaneous tissue disorders - Other, [skin sensitization] 
 
6.3 
Formulation and Stability 
Each packet (CHG and placebo) contains 2 cloths. The quantity of packets in each shipment 
will vary by the size of the patient. Each polyester cloth contains 500 mg chlorhexidine per 
cloth. The following inactive ingredients are included in each cloth: aloe vera, dimethicone, 
fragrance, glucono-delta-lactone, glycerin, Igepal®, polysorbate 20, propylene glycol, 
USP, and purified water. Chlorhexidine gluconate 2% cloths do not contain any alcohol. 
Store the product flat at controlled room temperature [between 20-25°C (68-77°F)]. Avoid 
excessive heat above 40°C (104°F). 
 
The placebo product for ACCL1034 will be similarly packaged and should be similarly 
stored.  
 
6.4 
Guidelines for Administration 
To open a package containing a cloth (for this trial only):  
• 
Hold the top of the package in one hand and lift flap on backside of package with 
the other hand. Grasp flap at top and pull down to tear flap along the middle (long 
axis) and expose blue foam insulator. Do not tear across the top.  
• 
Remove and discard the blue foam. 
• 
Take the cloths out one at a time. Do not remove the second cloth until the first 
cloth has been used and discarded. 
 
For external use only. Keep out of eyes and ears. Avoid contact with meninges; do not use 
as preparation for lumbar punctures. Discard each cloth after a single use. Once an individual 
package has been opened, the cloth must be used then discarded. If only one of the two cloths 
in the package is used, the other cloth must be discarded. Do not open and repackage cloths 
for future use. Do not microwave cloths. Do not flush cloths in the toilet. 
 
6.5 
Supplier 
Sage Products, Inc. Supplied by the Investigational Pharmacy Services of Seattle 
Children’s Hospital.  
 
 
7.0 
EVALUATIONS/MATERIAL AND DATA TO BE ACCESSIONED 
Timing of protocol therapy administration, response assessment studies, and surgical 
interventions are based on schedules derived from the experimental design or on established 
standards of care. Minor unavoidable departures (up to 72 hours) from protocol directed therapy 
and/or disease evaluations (and up to 1 week for surgery) for valid clinical, patient and family 
logistical, or facility, procedure and/or anesthesia scheduling issues are acceptable per COG 
administrative Policy 5.14 (except where explicitly prohibited within the protocol). 
 
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7.1 
Required Clinical, Laboratory and Disease Evaluations 
 
STUDIES TO BE OBTAINED 
Baselinea 
Study Period 
(90 days) 
History a 
X 
 
Ht, Wt, BSAa 
X 
 
Performance status a 
X 
 
MDRO and associated clinical data 
(MDRO worksheet) b, h 
X 
Each culture positive with a 
targeted organism 
Monitoring of patient census c 
 
X 
Patient cleansing diary d, h 
 
X 
Cleansing Cloth Use and Product 
Count Survey d 
 
At Day 45 and Day 90 (+/- 7 days) 
or at the time patient goes off 
protocol therapy 
Positive blood culture worksheet e, h 
 
Whenever the patient has a positive 
blood culture during the study 
period. 
Leftover bacterial isolates from 
patients with positive blood cultures 
during the study period f 
 
Whenever a patient has a positive 
blood culture during the study 
period. Should be monitored real-
time. 
Patient satisfaction questionnaire d, h 
 
At Day 90 (+/- 7 days) or at time 
patient goes off protocol therapy/off 
study 
Required Skin swabs (axilla and 
neck) for MDRO Acquisition and 
Resistance to CHG g 
X 
at Day 45 and Day 90 (+/- 7 days) 
Optional Nasal swabs and Perirectal 
or Stool Specimen swabs for 
MDRO Acquisition g 
X 
at Day 45 and Day 90 (+/- 7 days) 
a. This data and baseline swabs and data will be obtained prior to the start of cleansing. 
b. Can be assessed at Day 90 (retrospective) (See section 7.1.2 and 7.1.3).  
c. See product management document on protocol webpage for details. 
d. See section 7.1.6. 
e. Presence of positive blood cultures will be assessed real-time so that isolates can be 
collected. CLABSI will be defined using CDC criteria by coordinating site (Seattle) (see 
Sections 7.1.4 and 13.0 for details). This is ideally accomplished within 7 days after 
collection of the positive blood culture.  
f. Blood isolates to be saved every time a patient has a positive culture (See section 7.1.5 
for details. See section 13.2 for collection and shipping details). 
g. See section 14.0 for collection and shipping details.  
h. Once completed and received, must be uploaded into RAVE (See sections 7.1.3, 7.1.4, 
7.1.6.and 7.1.7). 
 
 
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7.1.1 
History and Demographic Information 
Demographic information collected at baseline will include age, gender, race, 
ethnicity, payment status, performance status, height, weight, cancer diagnosis, 
presence of down syndrome, presence of short bowel syndrome or severe 
malabsorption disorder, presence of colostomy or ileostomy, episodes of BSI 
within 30 days of enrollment, history of targeted organism (potential MDRO) 
within the last year, and number of days CHG bathing received in the 2 weeks prior 
to enrollment (0-14). For HCT recipients, the following will also be collected: cell 
source, donor type, donor HLA match, conditioning regimen, and reason for 
transplantation for benign conditions. 
 
7.1.2 
Clinical Care Data Collection 
Clinical care information will include any of the following that occur during the 
study period: number of positive blood cultures and number of positive cultures 
with a targeted organism (potential MDRO) with additional data for central review 
(see section 7.1.3 and 7.1.4), type of chemotherapy, type of radiation (TBI vs. 
focal), location of focal radiation, the number of days of radiation, dates of receipt 
of total parenteral nutrition (TPN), start and stop dates of periods of neutropenia 
(first day ANC < 500 and first day of 3 consecutive measurements with ANC 
> 500), dates of platelet transfusions, hospitalizations (admission and discharge 
dates), ICU admissions (admission and discharge dates), use of non-study CHG 
bathing while admitted in the ICU, dates and types of systemic antibiotics and/or 
antifungals including non-absorbable gut decontamination, and any clinical 
application of CHG for line accesses, line dressing changes, CHG impregnated 
line dressings (eg Biopatch etc.), and skin preparation for surgery; for HSCT 
patients, regimen for GVHD prophylaxis and treatment if any. For stratum 3 
patients that receive a transplant during the study period, the following will also 
be collected: cell source, donor type, donor HLA match, conditioning regimen, and 
GVHD prophylaxis and treatment if any. Clinical data collection on the CVC 
during the study period include date of CVC placement, type and size of CVC (the 
circumference in mm as reported by the “French Size” eg. 6 French Broviac etc), 
number of lumens of CVC, any clinical application of CHG during the line 
placement, date of CVC removals, reason for CVC removal, and dates of any CVC 
repairs.  
 
7.1.3 
Positive Cultures for MDRO 
The patient’s microbiology laboratory records will be reviewed for any cultures 
positive with a targeted organism (potential MDRO, see Appendix III) at any site 
that occurs during the study period and within 1-year prior to enrollment. A MDRO 
worksheet will be completed for each positive culture with a targeted organism 
(potential MDRO). Worksheets (paper) will be available on the protocol website. 
The worksheet includes date(s) of positive culture(s), site of culture(s), associated 
infection, and severity of infection (using CTCAE criteria). Worksheets should be 
completed and uploaded to RAVE. Additionally, microbiology laboratory records, 
complete with susceptibilities, must also be uploaded in RAVE along with the 
worksheet. Investigators at the coordinating site (Seattle) will review the 
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worksheet and microbiology laboratory results and determine if the targeted 
organism is a true MDRO and enter this data in RAVE. 
 
7.1.4 
Presence of CLABSI 
Patients will be monitored for positive blood cultures real-time. Data will be 
collected on all positive blood cultures that occur during the study period. A 
“positive blood culture” worksheet will be completed for each positive blood 
culture. Worksheets may be printed from the protocol website. The worksheet 
includes date and time of culture, presence of a central line, whether patients was 
hospitalized at time of positive culture, whether the patient had evidence of 
infection at another site of the body, whether the patient had a positive culture at 
another site of the body, and other information required for CLABSI 
determination. Worksheets should be completed and uploaded to RAVE within 7-
14 days after the positive blood culture (to allow time for other infections to be 
identified). Additionally, supporting microbiology laboratory records, complete 
with susceptibilities, must also be uploaded in RAVE along with the worksheet. 
Investigators at the coordinating site will review the worksheet and microbiology 
laboratory results and determine if the infection meets criteria for CLABSI using 
CDC definitions as outlined in section 13.1 and enter this data in RAVE.  
 
7.1.5 
Clinical Blood Culture Isolates 
Patients will be monitored for positive blood cultures real-time. Leftover positive 
clinical blood culture isolates will be retrieved from the clinical microbiology 
laboratories and sent to the coordinating site (Seattle) after the patient completes 
the study (See section 13.2 for details).  
 
7.1.6 
Cleansing Compliance Data 
7.1.6.1 Patient cleansing Diary 
Families will be given a daily diary formatted like a calendar where they 
will record whether study cleansing has taken place on a daily basis. Much 
of this trial will occur in the outpatient setting where the patient/family 
will be responsible for performing study cleansing. It is critical to be able 
to assess patient/family compliance with the intervention. Moreover, the 
daily diary conveys the importance of the intervention to families and will 
further engage them in the intervention. The diaries will be collected from 
the patients by the local research team at Day 45 and Day 90 at the time of 
swab collection. During periods of hospitalization, additional daily 
bathing diaries will be placed in the patient’s charts and completed by the 
clinical nurses. Families will continue to complete the patient diaries. 
Patient diaries and nursing diaries will be compared. Any discrepancies 
will be resolved by the local study team and the patient diary will be edited 
as necessary. Patient and Nursing diaries will be available in the starter 
packs provided to each site. Completed patient diaries will be uploaded to 
RAVE at Day 45 and at completion of the study. Nursing diaries will not 
be uploaded. Diary data will be reviewed by the coordinating site (Seattle). 
 
 
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7.1.6.2 Cleansing Cloth Use and Product count Survey: 
As an additional means to assess compliance, families will be contacted at 
day 45 and at completion of the study and a Cloth Use and Product Count 
Survey will be obtained. During the survey, families will be asked to 
provide a count of their remaining study product as well as provide the 
average number of baths missed since enrollment at Day 45 and since the 
last survey at Day 90 and provide the number of baths missed over the last 
week. Patients who go off protocol therapy (either prior to Day 45 or Day 
90) will complete a final cloth use and product count survey when they are 
removed from protocol therapy. 
 
7.1.6.3  Non-study Daily CHG Bathing 
Patients receiving protocol-therapy in either arm should not use non-study 
CHG products (CHG cloths or liquid CHG soap) for daily bathing. 
Patients should only use approved CHG products as outlined in sections 
4.2.1-4.2.3. Use of any non-study CHG bathing will be assessed using the 
daily diary. 
 
7.1.7 
Use of compatible soaps and lotions & patient satisfaction questionnaire 
Study participants can only use CHG compatible soaps on areas except the face 
and hand during study cleansing days. Any soap may be used to wash the hands or 
face. Additionally, only CHG compatible lotions can be applied to areas except the 
face and hand during study cleansing days. Any lotion can be applied to the hands 
or face. Incompatible soaps and lotions may inactivate CHG. Each starter pack and 
subsequent product shipment will include CHG compatible soap and lotion for 
each participant. If a family wishes to use their own soaps and lotions they may do 
so if they are CHG compatible. A comprehensive list of commercially available 
compatible products is located on the protocol webpage. If an institution or family 
wishes to use a soap or lotion and compatibility is unknown, see ‘Product 
Management’ document on the protocol webpage for additional information. Use 
of products other than those provided by the study will be assessed using the daily 
diary and the patient satisfaction questionnaire referenced below. 
 
At Day 90 or when the patient is off protocol therapy/off study, study staff will 
administer a questionnaire to the family to assess usability of the study cloths and 
satisfaction with the product. This questionnaire will be a paper form (available on 
the protocol webpage) that can be administered in person or over the phone. 
Completed questionnaires must be uploaded to RAVE for review.  
 
7.1.8 
Skin Swabs 
Skin swabs (neck and axilla) will be collected at baseline, Day 45 (+/- 7 days) and 
Day 90 (+/-7 days) to assess CHG and antimicrobial resistance in skin 
microorganisms and changes in MDRO colonization. These should be sent to the 
coordinating site (Seattle) within 24 hours. See section 15.0 for details. 
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7.2 
Optional Study 
As part of the ACCL1034 trial, an ancillary study will assess whether CHG cleansing 
decreases acquisition MDRO in children with cancer those receiving allogeneic HCT. 
Nasal and perirectal swabs (or stool samples) will be collected at baseline, Day 45 (+/- 7 
days) and Day 90 (+/- 7 days) to assess changes in MDRO colonization.  
 
All patients enrolled in ACCL1034 will be offered the opportunity to participate in this 
ancillary study. Presence of MDRO will be determined by nasal and perirectal swabs (or 
stool samples). Perirectal swabs are preferred to stool samples in many COG institutions 
and have increased sensitivity for detecting MRSA. Consequently, perirectal swabs will be 
the preferred method of MDRO screening, although an institution or individual patient may 
choose to use stool specimens as long as the method of collection is consistent within an 
individual patient. If a stool specimen cannot be provided during a sampling period (such 
as constipation), a perirectal swab may be substituted. 
 
 
8.0 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY 
CRITERIA 
8.1 
Criteria for Removal from Protocol Therapy 
a) A problem with skin integrity (generalized skin breakdown such as severe skin GVHD 
or other severe generalized skin disruption) judged by the attending physician to 
warrant discontinuation of study treatment. 
b) Any skin reaction thought to be caused by allergy to the cleansing product.  
c) Any non-allergic skin reaction > Grade 3 possibly, probably, or definitely related to 
the cleansing product.  
d) Patient receives Sorafenib after study enrollment. 
e) Physician determines it is in the patient’s best interest. 
f) Emergency un-blinding. 
g) Refusal of further protocol therapy by patient/parent/guardian. 
 
Patients who are off protocol therapy are to be followed for positive blood cultures, targeted 
organisms (potential MDRO), all clinical data collection outlined in section 7.1.2, swab 
collection, and continuation of daily diary until they meet the criteria for Off Study (see 
below).  
 
8.2 
Off Study Criteria 
a) Withdrawal of consent for any further data submission 
b) Death 
c) Completion of planned study assessments 
d) Enrollment onto COG study ACCL0934 
e) Lost to follow up 
 
 
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9.0 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Design 
This study is a randomized, double blind study that aims to examine the effect of CHG 
cleansing on occurrence of CLABSIs (primary aim), acquisition of MDRO, susceptibility 
to CHG, and bacteremia in pediatric patients with cancer or those receiving an allogeneic 
HCT. Randomization between CHG and control cleansing will be stratified by 
myeloablative or reduced intensity allogeneic transplantation versus non-myeloablative 
allogeneic transplantation versus oncology patients receiving chemotherapy with or 
without subsequent transplantation. 
 
9.2 
Patient Accrual and Expected Duration of Trial 
The study aims to accrue up to 450 patients, age 2 months to 21 years, with a planned CVC 
for at least 3 months. We do not have a good estimate for the expected COG accrual rate on 
this study as we have no prior COG studies on similar patients. As we estimate that the 
potential patient pool with such CVC duration should be large hundreds per year within COG), 
we anticipate accruing 450 patients in 4 years. 
 
9.3 
Statistical Analysis Methods 
9.3.1 
Study Endpoints 
The primary endpoint is the number of CLABSI events during the at-risk days 
(within the 90-day study period). Days that the patient is at risk for CLABSI are 
defined as the days when the patient has an eligible CVC plus 2 days following the 
loss of an eligible tunneled CVC. In other words, an event occurred during the 
2 days immediately following the loss of an eligible CVC (without a replacement) 
will be attributed to the lost CVC. CLABSI will be defined by a central review 
committee blinded to the study treatment (see Section 13). 
 
Secondary endpoints include acquisition of MDRO, susceptibility to CHG, and the 
number of bacteremia episodes during the at-risk days. 
 
9.3.2 
Sample Size and Power Consideration 
For the primary endpoint of CLABSI, rates of 3.3 - 4.6 CLABSI per 1000 catheter 
days have been documented in pediatric patients with cancer.39,40 Higher risk 
diagnoses, such as AML, however, have much higher rates of CLABSI. Assuming 
the patients in the control arm have a constant rate of CLABSI at 5 per 1000 
catheter days compared to a constant rate of 3 per 1000 catheter days in the CHG 
arm, 400 patients (200 per arm) will provide at least 85% power in a Poisson 
regression model to detect the difference in the rate of CLABSI between the 2 arms 
at 2-sided alpha of 0.05 if all patients have 90 at-risk days for CLABSI. Power 
estimation is based on simulations. The maximum enrollment is increased to 450 
randomized patients to account for ineligible enrollments and loss of at-risk days 
in some patients during the 90-day period because of days without a CVC. 
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Based on the effective sample size of 200 per arm with 90 at-risk days, for the 
secondary endpoint of bacteremia, assuming a constant rate of 7 per 1000 catheter 
days in the control arm compared to 4.5 per 1000 catheter days in the CHG arm, 
the study will provide at least 88% power in a Poisson regression model for 
detecting the reduction in the rate of bacteremia at 2-sided alpha level of 0.05.  
 
For the secondary endpoint of acquisition of MDRO, the power estimation is based 
on comparing the percentage of patients with MDRO acquisition between the 2 
arms. Estimates for MDRO acquisition are lacking in pediatric oncology patients. 
Assuming 15% of patients in the control arm acquire MDRO, with 200-225 
patients per arm, the study will provide 84-88% power for detecting a 6% MDRO 
acquisition in patients in the CHG arm (a decrease of 9% from the control arm); if 
20% of the patients in control arm acquire MDRO, the power will be 80-85% for 
detecting a 10% MDRO acquisition for patients in the CHG arm (a decrease of 
10% from the control arm). 
 
For the secondary endpoint on susceptibility to CHG, the power estimation is based 
on comparing the percentage of patients with blood culture or swab that shows 
reduced susceptibility to CHG (defined by MIC and MBC cutoffs) between the 2 
arms. Assuming 5% of patients in the control arm have reduced susceptibility of 
CHG, with 200-225 patients per arm, the study will provide 80-85% power for 
detecting a 13% patients with reduced susceptibility to CHG in the CHG arm (an 
increase of 8% compared to the control arm); if 10% of the patients in control arm 
have reduced susceptibility to CHG, the power will be 80-85% for detecting 20% 
patients with reduced susceptibility in the CHG arm (an increase of 10% compared 
to the control arm). 
 
9.3.3 
Analysis Plan 
The primary analysis for CLABSI will be based on intent-to-treat analysis. The 
rate of CLABSI when the patient is at risk will be estimated and compared between 
the 2 arms by a Poisson regression model adjusting for the randomization 
stratification factor on treatment/diagnosis. Patient specific at-risk days will be 
included as offset in the Poisson regression. We will also consider adjustment for 
potential confounders and potential interaction between risk factors and treatment 
in the analysis. Secondary analyses of time to first CLABSI event will be 
performed using survival analysis methodology including log rank test and Cox 
proportional hazards models. Such analyses include only the first CLABSI event 
rather than all events. They are useful alternative approaches as the delay of first 
CLABSI is clinically important and the chance of multiple CLABSI events is 
expected to be low. Given the expected rate of CLABSI, the chance of a patient 
having more than one qualifying event during the study period should be small. If 
we observe a higher than expected number of patients having multiple CLABSI, 
we will examine the risk for second or later events to see if there are any 
suggestions of a higher risk than that for the first event.  
 
 
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The study will also examine whether CHG cleansing changes the acquisition of 
new MDRO by Day 45 (half way through the treatment period) and by the end of 
the study. Clinical data reported by the site as well as swab specimens analyzed by 
the coordinating site (Seattle) will be used to determine acquisition of 
epidemiologically important MDRO. Patients with a past infection or known 
colonization status with a particular MDRO will not be able to acquire that MDRO 
at a later time during the study period. The consequence is that later outcomes are 
actually determined by previous outcomes. Such a deterministic relationship 
makes a longitudinal analysis of MDRO status at all 3 time points (baseline, Day 
45, and Day 90) infeasible, therefore we will evaluate acquisition of 
epidemiologically important MDRO by Day 45 and by the end of the study (if a 
patient is infected or colonized by Day 45, then the patient is also considered 
infected or colonized by the end of the study). The effect of CHG cleansing on the 
proportion of patients acquiring MDRO by Day 45 or by the end of the study will 
be compared between the two arms using logistic regression, adjusting for the 
randomization stratification factor on treatment/diagnosis and other potential 
confounders such as baseline patient characteristics. Non-linear mixed effects 
models will also be used to examine the effect of CHG on the proportion of patients 
acquiring MDRO with adjustment for the treating institution as random effects. 
This outcome will be evaluated in aggregate as well as by organism (MRSA, VRE, 
etc.). In addition, this outcome will be evaluated using data from the swabs alone.  
 
This study will also evaluate whether use of CHG is associated with skin and 
bloodstream microorganisms demonstrating reduced susceptibility to CHG, which 
will be measured by MICs and MBCs. Analyses will be done separately for skin 
and bloodstream isolates. For skin isolates, MIC and MBC medians, interquartile 
ranges, and ranges will be described for each arm at baseline, Day 45, and Day 90 
time points for S. aureus and coagulase negative staphylococci in aggregate and 
separately. We will describe the frequency of patients in each arm with a skin 
isolate demonstrating reduced susceptibility to CHG (defined both by MIC and 
MBC) at each time point. Comparison of CHG susceptibility status from skin 
isolates (yes/no based on chosen cutoff point) across study arms at Day 45 and Day 
90 will be based on logistic regression, with adjustment for the randomization 
stratification factor on treatment/diagnosis and other potential confounders. In 
addition, we will apply nonlinear mixed models to explore the association between 
CHG cleansing and reduced susceptibility to CHG over the longitudinal 
assessments. These models will account for the correlation of repeated measures 
over time. We will also evaluate the association between reduced susceptibility to 
CHG and resistance to commonly used antimicrobials in cutaneous staphylococci, 
overall and by species, using both chi-square test and logistic regression where 
resistance to commonly used antimicrobials will be modeled as the outcome and 
reduced susceptibility to CHG as the predictor of interest. We will stratify analyses 
by whether or not qacA/B was detected. For bloodstream isolates, we will compare 
the frequency of bloodstream isolates resistant to CHG at any time during study 
period between those who received CHG cleansing versus those who received 
control cleansing using similar analysis as described above.  
Daily compliance data based on the patient diary on whether protocol cleansing 
was completed (and if not, the reason) and on usage of unauthorized soap and 
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location will be captured. In addition, product count and an estimate by the family 
for number of missed cleansing will be obtained at day 45 and at completion of 
study. We will describe the compliance with protocol-cleansing/usage of 
unauthorized soap or location and the reasons for missed protocol cleansing using 
appropriate summary and descriptive statistics. Summary variable on compliance 
with protocol cleansing or on usage of unauthorized soap/location will be created, 
such as the number/percentage of days with compliance or a binary variable for 
compliance based on a cutoff. We will examine whether there are differences in 
compliance between the 2 arms on such summary compliance variables by 
appropriate two sample tests. We will also include such summary compliance 
variables in the regression models as covariate to explore whether the treatment 
effect of CHG is associated with such compliance measures. 
 
Descriptive statistics will be used to summarize the responses to the patient 
satisfaction survey collected at the end of the study. Counts/percentages of patients 
who consider the study cleansing easy/difficult to use and those of patients 
satisfied/unsatisfied with the cleansing cloths will be tabulated. The reasons 
provided for dissatisfaction will also be tabulated. These descriptive statistics will 
be generated for the entire study population across the 2 arms first and then by 
each arm. 
9.3.4 
Interim monitoring 
Interim efficacy monitoring on the rate of CLABSI will be performed once after 
about half of the patients complete study observation. Monitoring boundary will 
be based on Lan-Demet’s method with spending function αt2. No interim futility 
monitoring is planned because reduction in the risk of MDRO acquisition, if any, 
is also considered an important effect of CHG even if the rate of CLABSI is not 
reduced by CHG cleansing. Informal interim analysis on incidence and severity of 
skin rash will be performed annually. If such informal analysis suggests a 
significantly higher incidence of rash for CHG patients compared to the control 
patients at the alpha level of 0.05, the study committee will perform a review of 
the data on rash and report the findings and study committee recommendation to 
the DSMC. The DSMC may also make their assessment and recommendation 
regarding the study at any time. 
9.3.5 
Potential Confounders and Effect Modification Factors  
Potential confounders that influence the underlying risk of CLABSI and factors 
that may modify the effect of CHG treatment will be collected on the study 
participants. Such factors include some patient and/or disease characteristics as 
well as clinical care practices. These data collection are described in Section 7.1.1 
and Section 7.1.2. These factors will be explored in the adjusted regression 
analyses. Such potential confounders and effect modification factors on patient or 
disease characteristics will be considered for inclusion as covariates in the Poisson 
regression models for analyzing incidence of CLBASI and in the logistic 
regression models and nonlinear mixed models for analyzing acquisition of 
MDRO or reduced susceptibility to CHG at Day 45 and Day 90. Time-dependent 
factors will be considered for inclusion as time-dependent covariates in analyzing 
time to first CLABSI; for acquisition of MDRO or reduced susceptibility to CHG 
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at Day 45 and Day 90, these time-dependent factors prior to Day 45 and Day 90 
will first be summarized and the summary variables be considered as covariates in 
the modeling. Alternative modeling of CLABSI incidence which might 
accommodate time-dependent factors will also be explored. One possible approach 
might be to model the daily outcome on CLABSI as a binary variable with 
dependence within patients across the daily outcomes, and to incorporate some 
summary variable for the time-dependent factors up to the particular day as 
covariate for the binary outcome. 
 
9.4 
Gender and Minority Accrual Estimates 
The gender and minority distribution of the study population is expected to be: 
 
 
Accrual Targets 
 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
44 
66 
110 
Not Hispanic or Latino 
129 
211 
340 
Ethnic Category: Total of all subjects 173 
277 
*450 
Racial Category 
 
American Indian or Alaskan Native 
2 
1 
3 
Asian 
5 
9 
14 
Black or African American 
18 
37 
55 
Native Hawaiian or other Pacific 
Islander 
0 
5 
5 
White 
148 
225 
373 
Racial Category: Total of all subjects 173 
277 
*450 
* These totals must agree 
 
The estimates are based on Children’s Oncology Group (COG) patient demographics, 
assuming 15% of subjects with acute myeloid leukemia (AML) (race/gender distribution 
estimated from AAML0531), 35% of subjects with relapsed acute lymphoblastic leukemia 
(ALL) (projected race/gender distribution for AALL07P1), and 50% of subjects being 
allogeneic hematopoietic cell transplant recipients (race/gender distribution estimated from 
allogeneic transplant patients on ACCL0331). 
 
 
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10.0 
EVALUATION CRITERIA  
10.1 
Common Terminology Criteria for Adverse Events (CTCAE) 
This study will utilize version 4.0 of the CTCAE of the National Cancer Institute (NCI) for 
toxicity and performance reporting. A copy of the CTCAE version 4.0 can be downloaded 
from 
the 
CTEP 
website 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm). 
Additionally, toxicities are to be reported on the appropriate case report forms. 
 
Please note: ‘CTCAE v4.0’ is understood to represent the most current version of CTCAE 
v4.0 as referenced on the CTEP website (i.e., v4.02 and all subsequent iterations prior to 
version 5.0). 
 
 
11.0 
ADVERSE EVENT REPORTING REQUIREMENTS 
11.1 
Purpose 
Adverse event data collection and reporting, which are required as part of every clinical 
trial, are done to ensure the safety of patients enrolled in the studies as well as those who 
will enroll in future studies using similar agents.  
11.2 
Determination of Reporting Requirements 
Reporting requirements may include the following considerations: 1) the characteristics of 
the adverse event including the grade (severity); 2) the relationship to the study therapy 
(attribution); and 3) the prior experience (expectedness) of the adverse event. 
 
Commercial agents are those agents not provided under an IND but obtained instead from 
a commercial source. In some cases an agent obtained commercially may be used for 
indications not included in the package label. In addition, NCI may on some occasions 
distribute commercial supplies for a trial. Even in these cases, the agent is still considered 
to be a commercial agent and the procedures described below should be followed. 
 
Determine the prior experience Expected events are those that have been previously 
identified as resulting from administration of the agent. An adverse event is considered 
unexpected, for reporting purposes only, when either the type of event or the severity of 
the event is not listed in:  
 
• 
the current known toxicities for each commercial agent as provided in the 
Drug Information for Commercial Agents Used by the Children’s 
Oncology Group posted on the COG website; or 
• 
the drug package insert. 
11.3 
Reporting of Adverse Events for Commercial Agents - via CTEP-AERS 
Expedited AE reporting must use CTEP-AERS (Adverse Event Expedited 
Reporting System), accessed via https://eapps-ctep.nci.nih.gov/ctepaers 
 
Commercial reporting requirements are provided in Table B. The commercial agent(s) used 
in this study are listed in the front of this protocol immediately following the Study 
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Committee roster. 
• 
COG requires the CTEP-AERS report to be submitted within 5 calendar 
days of learning of the event. 
• 
Use the NCI protocol number and the protocol-specific patient ID provided 
during trial registration on all reports. 
 
CTCAE term (AE description) and grade: The descriptions and grading scales found in 
the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be 
utilized 
for 
AE 
reporting 
and 
are 
located 
on 
the 
CTEP 
website 
at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
All 
appropriate treatment areas should have access to a copy of the CTCAE. 
 
Table B  
Reporting requirements for adverse events experienced by patients on study 
who have NOT received any doses of an investigational agent on this study. 
 
CTEP-AERS Reporting Requirements for Adverse Events That Occur During 
Therapy with a Commercial Agent or Within 30 Days1 
Attribution 
Grade 4 
Grade 5 
 
Unexpected 
Expected 
 
Unrelated 
or 
Unlikely 
 
 
CTEP-AERS 
Possible, 
Probable, 
Definite 
CTEP-AERS 
 
CTEP-AERS 
1This includes all deaths within 30 days of the last dose of treatment with a 
commercial agent, regardless of attribution. Any death that occurs more than 
30 days after the last dose of treatment with a commercial agent that can be 
attributed (possibly, probably, or definitely) to the agent and is not due to 
cancer recurrence must be reported via CTEP-AERS. 
 
11.4 
Routine Adverse Event Reporting 
Note: The guidelines below are for routine reporting of study specific adverse events on 
the COG case report forms and do not affect the requirements for CTEP-AERS reporting. 
 
The NCI defines both routine and expedited AE reporting. Routine reporting is 
accomplished via the Adverse Event (AE) Case Report Form (CRF) within the study 
database. For this study, routine reporting will include all CTEP-AERS reportable events 
and all Grade > 1 CTCAE v.4 skin reactions (System Organ Class “Skin and Subcutaneous 
Tissue Disorders”) with the following adverse event headings: skin induration, skin 
ulceration, rash maculo-papular, urticaria, skin and subcutaneous tissue disorders – others, 
specify, stevens-johnson syndrome and toxic epidermal necrolysis.  
 
 
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12.0 
RECORDS AND REPORTING 
See the Case Report Forms posted on the COG web site with each protocol under “Data 
Collection/Specimens”. A submission schedule is included. 
 
12.1 
CDUS 
This study will be monitored by the Clinical Data Update System (CDUS). Cumulative 
CDUS data will be submitted quarterly to CTEP by electronic means. Reports are due 
January 31, April 30, July 31 and October 31. This is not a responsibility of institutions 
participating in this trial. 
 
 
13.0 
Central Line Associated Bloodstream Infection (CLABSI) and collection of left over 
clinical blood culture isolates 
Patients will be followed for positive blood cultures real-time. Each positive blood culture will 
prompt collection of the data necessary to determine whether it meets criteria for CLABSI as 
defined by CDC criteria (see appropriate case report form for variables to collect). Determination 
of CLABSI will be accomplished by 2 investigators blinded to the cleansing product that the subject 
is receiving. Additionally, the 2 investigators will be blinded to each other’s responses while 
making this determination. Discordant decisions will be resolved by consensus. Final 
determinations will be recorded on the central review form by the coordinating site (Seattle). 
Peripheral blood culture is not required to perform this classification. The clinical blood isolate will 
be sent to Seattle for further testing. 
  
13.1 
CDC Criteria for Central Line Associated Bloodstream Infection (CLABSI). To be 
used by the investigators coding CLABSI 
Investigators will use the most current CDC definition for coding CLABSI. 
13.1.1 Additional considerations not included in the CDC criteria 
 
a. We will include criteria for recurrence of infection and recurrent infections will 
not be counted as new infections. These criteria will include: 1) the subsequent 
positive culture occurs in association with the same CVC as the previous infection 
(the CVC was not replaced with the previous infection), 2) the subsequent positive 
culture is due to the same organism/s as the previous infection without new 
organism/s cultured, and 3) the subsequent positive culture occurs within 4 weeks 
of the first infection. All 3 criteria must be present for a positive culture to be 
deemed a recurrent infection. Different species isolated within a week of an initial 
isolate will be counted as one infection episode. Different species identified at least 
one week after the initial isolate will be categorized as a new infection. 
 
 
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13.2 
Positive clinical blood culture isolates 
13.2.1 Sample collection 
Any positive blood cultures that occur during the study period will be sent to 
Seattle for CHG and antimicrobial susceptibility testing. See the laboratory manual 
on the protocol webpage for additional information. 
 
13.2.2 Obtaining clinical blood culture samples 
• 
Use a sterile cotton swab to touch 2-5 colonies of pure growth on Sheep Blood 
or MacConkey Agar. 
• 
Place swab in cryovial with 1 ml of BBL trypticase Soy Broth with 20% 
glycerol (or freezing media of your choice) and agitate.  
• 
Remove swab and freeze liquid sample in cryovial at -70ºC.  
• 
Isolates will be affixed with a freezer-safe label provided by the coordinating 
site (Seattle).  
• 
Isolates will be labeled with the protocol number, patient’s COG ID number, 
BPC number and date of collection. 
 
13.2.3 Sample shipping. 
Blood culture samples will be shipped to Seattle for further testing. Each center 
will use shipping kits provided by Seattle Children’s. These kits will contain a 
Styrofoam-line insulated shipper, biohazard bag, isolate shipping inventory sheet 
 
Shipping form: Complete an isolate shipping inventory sheet for each isolate in the 
shipment. Site should retain copies. 
 
Packaging: 
• 
Assure all specimens are labeled correctly and legibly. 
• 
Place all labeled isolates in the biohazard bag and seal. The biohazard bag is 
provided in the shipping kit. 
• 
Ship isolates in the box provided in the shipping kit along with 3kg of dry ice. 
• 
Place the biohazard bag containing the isolates in the box and surround with 
dry ice. 
• 
Replace the Styrofoam lid on the box but do not tape the lid of the Styrofoam 
box. 
• 
Place the completed isolate shipping inventory sheet on top of the Styrofoam 
liner. 
• 
Tape the cardboard box. 
 
Shipping Instructions: 
• To optimize efficiency, these specimens should be shipped at the end of the 
patient’s participation (day 90 or when the patient is off study).  
• Ship isolates on Monday-Friday. Friday shipments must be completed prior to 
final FedEx pick-up time at the respective site. Please do not ship the day 
preceding a holiday.  
 
 
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• Fax a shipment notification form located on the protocol page to the Qin 
laboratory at Seattle Children’s Hospital (see Specimen Shipping forms on the 
protocol webpage).  
• All isolates are shipped via FedEx Priority Overnight. 
• Generate a shipping label via the FedEx website (www.fedex.com). Account 
information is provided on the shipment notification form that can be found 
on the protocol webpage. 
 
• Ship specimens to : 
Dr. Xuan Qin 
4800 Sandpoint Way NE, A-6901 
Seattle, WA 98105 
Phone: (206) 987-2586  
Fax: (206) 987-3840 
Contact: Jessica Berry jessica.berry@seattlechildrens.org 
 
 
14.0 
MDRO Data Collection 
Historical and ongoing clinical cultures will be used to determine acquisition of epidemiologically 
important MDRO. In addition, to enhance sensitivity of MDRO detection, nasal and perirectal 
swabs will be obtained at baseline and 45 and 90 days after enrollment (See Section 15). Patients 
with any past cultures or a baseline swab positive for MDRO will be designated as a known MDRO 
carrier. MDRO acquisition will be defined by any positive clinical culture or screening swab 
cultures obtained subsequent to the baseline swab in a patient that is not an MDRO carrier. MDRO 
will be analyzed in aggregate and for each organism separately (MRSA, VRE, etc.). An MDRO 
worksheet will be completed for any positive culture with a targeted organism (potential MDRO). 
Both historical (year prior to enrollment) and occurrences during the study period will be collected. 
Data included on the MDRO worksheet includes culture date, culture site, clinical information 
regarding infection, severity of infection (if obtained during the study period). Completed 
worksheet as well as the microbiology laboratory record, including susceptibilities, will be 
uploaded to RAVE. The coordinating site will evaluate the worksheet and microbiology laboratory 
results and determine if the targeted organism is a true MDRO. Central review forms will be 
completed by the coordinating site for those judged to be true MDRO. 
14.1 
Any cultures with the targeted organisms listed in Appendix III will be evaluated as 
potential MDRO.  
 
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15.0 
SPECIMEN REQUIREMENTS 
 
15.1 
Screening Swabs 
The screening swabs (nares, axilla and neck, and perirectal) will be obtained at study entry 
(before day 1 of cleansing), Day 45, and at Day 90. The swabs will be processed for the 
bacterial counts, MDRO and CHG resistance.  
Screening swabs will be collected using kits provided by Seattle Children’s Hospital. Each 
kit will contain: 
1) Three (3) Copan swabbing systems in 1mL bacterial transport media; 
2) 3 ampules of saline;  
3) Labels; 
4) A plastic biohazard bag; and 
5) Instructions for obtaining swabs (See Section 15.1.1). 
 
15.1.1 Swab Collection 
Each swab should be collected as follows. A detailed instruction sheet is also 
available on the protocol webpage. 
 
Axilla and Neck (Required study) 
1) Remove the swab from the pouch. 
2) Moisten the swab with the saline. 
3) Rub the swab on the side or back of the neck over a 3x3cm area, for 20 seconds. 
4) Rub the same swab in the axilla over a 3x cm area, for 20 seconds. 
5) Remove the lid from the vial containing the bacterial transport media.  
6) Place the swab all the way to the bottom of the tube, place the swab against the 
side of the vial and break the applicator shaft at the molded breakpoint (marked by 
a pink line). Screw the cap down tightly on the vial.  
7) Label the tube with the patient’s study ID number, collection date, and collection 
site (skin). 
8) Place the labeled tube in the biohazard bag. 
 
Nares (Optional study) 
1) Remove the swab from the pouch. 
2) Moisten the swab with the saline. 
3) Rotate the swab 5x clockwise and counterclockwise in each anterior nare 
(nostril). 
4) Remove the lid from the vial containing the bacterial transport media.  
5) Place the swab all the way to the bottom of the tube, place the swab against the 
side of the vial and break the applicator shaft at the molded breakpoint (marked by 
a pink line). Screw the cap down tightly on the vial.  
6) Label the tube with the patient’s study ID number, collection date, and collection 
site (nares). 
7) Place the labeled tube in the biohazard bag. 
 
 
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Perirectal/stool (Optional study) 
1) Remove the swab from the pouch. 
2) Moisten the swab with the saline. 
3) Using the swab from the saline system, gently rub the swab in the perirectal 
region for 20 seconds. If obtaining a stool swab, dip the swab directly in the stool 
sample. 
4) Remove the lid from the vial containing the bacterial transport media.  
5) Place the swab all the way to the bottom of the tube, place the swab against the 
side of the vial and break the applicator shaft at the molded breakpoint (marked by 
a pink line). Screw the cap down tightly on the vial.  
6) Label the tube with the patient’s study ID number, collection date, and collection 
site (perirectum or stool). 
7) Place the labeled tube in the biohazard bag. 
15.1.2 Sample Processing 
As a means to ensure the highest level of bacterial recovery, swabs should be 
shipped to Seattle Children’s Hospital on the day they are collected. If that is not 
possible, they should be refrigerated overnight and shipped no later than the next 
day. Swabs can be shipped Monday-Friday. If shipping on Friday, shipments must 
me made prior to the last FedEx pick-up time at the respective site. 
15.1.3 Shipping 
• 
Swabs will be shipped using kits provided by Seattle Children’s Hospital. Each 
kit will contain a Styrofoam lined shipping box, cold pack, and swab shipping 
inventory sheet.  
• 
Shipping form: Complete a swab shipping inventory sheet for each isolate in 
the shipment. Site should retain copies. 
 
Packaging: 
• 
Assure all specimens are labeled correctly and legibly. 
• 
Assure all specimens are in a sealed plastic biohazard bag. 
• 
Ship isolates in the box provided in the shipping kit along with the cold pack 
that should be frozen. 
• 
Place the frozen cold pack into the Styrofoam liner. This cold pack will ensure 
specimen integrity during overnight shipping. 
• 
Place the plastic biohazard bag containing the swabs directly on top of the 
frozen cold pack. 
• 
Replace the Styrofoam lid on the box. 
• 
Place the completed swab shipping inventory sheet on top of the Styrofoam 
box. 
• 
Tape the cardboard box. 
 
 
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Shipping Instructions: 
• 
Ship isolates on Monday-Friday. Friday shipments must be completed 
prior to final FedEx pick-up time at the respective site.  
• 
Please do not ship the day preceding a holiday.  
• 
Fax a shipment notification form located on the protocol page to the Qin 
laboratory at Seattle Children’s Hospital (see Specimen Shipping forms 
on the protocol webpage).  
• 
All isolates are shipped via FedEx Priority Overnight. 
• 
Generate a shipping label via the FedEx website (www.fedex.com).  
• 
Account information is provided on the shipment notification form that 
can be found on the protocol website. 
 
 
 
 
 
 
 
 
 
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APPENDIX I: Definitions for the Intensity of a Hematopoietic Stem Cell Transplant 
Conditioning Regimen 
 
In order to assist in the proper classification of SCT Conditioning Regimens for stratification purposes, 
please utilize the following definitions.41  
 
1. Myeloablative: A combination of agents expected to produce profound pancytopenia and 
myeloablation within 1-3 weeks from administration; pancytopenia is long lasting, usually 
irreversible, and in most instances fatal, unless hematopoiesis is restored by hematopoietic stem 
cell infusion.  
Examples: 
a. Total Body Irradiation (TBI) ≥5 Gy as a single dose or ≥8 Gy a fractionated doses, 
generally in combination with other agents 
b. Busulfan >8 mg/kg total dose, generally in combination with other agents 
 
2. Non-myeloablative (also termed "Immunoablative”): A regimen that will cause minimal cytopenias 
and does not require stem cell support.  
Examples: 
a. TBI ≤2 Gy ± a purine analog (i.e. Fludarabine) 
b. Fludarabine + Cyclophosphamide ± Serotherapy (ATG or Alemtuzumab) 
c. Fludarabine + Cytarabine + Idarubicin 
d. Cladribine + Cytarabine 
e. Total Lymphoid Irradiation + Serotherapy 
 
3. Reduced intensity (also termed “RIC”): A regimen that cannot be classified as non-myeloablative 
or myeloablative. 
Examples: 
a. Fludarabine + Melphalan ≤140 mg/m2  
b. Cyclophosphamide 200 mg/kg ± Serotherapy 
 
If it is not clear what definition should be applied to a specific conditioning regimen, centers are encouraged 
to discuss with the Study Chair and Committee prior to enrollment in order to ensure uniformity of the 
stratification system. 
 
 
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APPENDIX II: STANDARDIZED INSTRUCTIONS FOR USE OF STUDY CLEANSING 
CLOTHS 
 
(Package label) 
 
 
 
 
 
• Cloths can be used at room temperature or warmed.  
• DO NOT microwave cloths. 
• If warm cloths are preferred, fill a large bowl or basin with warm water (temperature 
you would use for bathing) and immerse the pack of cloths in water and hold for 30-60 
seconds. OR, if hospitalized, an appropriate warmer may be used. ONLY use warmers 
that are designed for bathing cloths. 
• KEEP Cloths out of eyes, ears, and mouth.  Use regular approved soap for washing the 
face. 
• Wipe the cloths in a circular or back and forth motion over the part of the body to be 
cleaned.  Use the chart below to determine which part of the body should be cleaned with 
each cloth. 
• DO NOT rinse the skin. 
• DO NOT apply any unapproved lotions.  
• DO NOT apply more than once/day. If second bath is needed, use water and approved 
soap. 
• If a regular soap and water bath is desired on a routine basis, use the study cloths after 
the regular bath.  After the soap and water bath, allow the skin to cool for a few minutes 
before using the study cloths. 
 
 
<22lbs (10kg) 
22-66lbs (10-30kg) >66lbs (>30kg) 
CHG Cloth 1 Neck, Chest, Abdomen,  
Both Arms, and Back 
Neck, Chest, Abdomen
 and Both Arms 
Neck, Chest, Abdomen 
CHG Cloth 2 Both Legs, Buttocks, and 
Genital/anal area 
Back and Buttocks 
Both Arms 
CHG Cloth 3 ------------------- 
Both Legs 
Right Leg 
CHG Cloth 4 ------------------- 
Genital/anal Area 
Left Leg 
CHG Cloth 5 ------------------- 
--------------------- 
Back and Buttocks 
CHG Cloth 6 ------------------- 
-------------------- 
Genital/anal Area 
 
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APPENDIX III: TARGETED ORGANISMS 
• 
Staphylococcus aureus- resistant to oxacillin, nafcillin, or methicillin 
• 
Enterococcus faecalis or Enterococcus faecium resistant to vancomycin 
• 
Escherichia coli (E. coli) resistant or intermediately susceptible to ceftriaxone, ceftazidime, 
cefepime or any carbapenem (meropenem, imipenem, ertapenem) OR those identified by your 
laboratory as being multi-drug resistant or “ESBL” organisms 
• 
Klebsiella pneumoniae or Klebsiella oxytoca resistant or intermediately susceptible to 
ceftriaxone, ceftazidime, cefepime or any carbapenem (meropenem, imipenem, ertapenem) OR 
those identified by your laboratory as being multi-drug resistant or “ESBL” organisms 
• 
Any Serratia, Enterobacter, or Citrobacter species resistant or intermediately susceptible to 
cefepime or any carbapenem (meropenem, imipenem, ertapenem) 
• 
Any Acinetobacter baumannii  
• 
Any Pseudomonas aeruginosa  
• 
Any Clostridium difficile  
 
 
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APPENDIX IV: CTEP REGISTRATION PROCEDURES 
CTEP Investigator Registration Procedures 
Food and Drug Administration (FDA) regulations and National Cancer Institute (NCI) policy 
require all investigators participating in any NCI-sponsored clinical trial to register and to renew 
their registration annually. 
 
Registration requires the submission of: 
 
• 
a completed Statement of Investigator Form (FDA Form 1572) with an original signature 
• 
a current Curriculum Vitae (CV) 
• 
a completed and signed Supplemental Investigator Data Form (IDF) 
• 
a completed Financial Disclosure Form (FDF) with an original signature 
 
Fillable PDF forms and additional information can be found on the CTEP website at 
<http://ctep.cancer.gov/investigatorResources/investigator_registration.htm>. For questions, please 
contact 
the 
CTEP 
Investigator 
Registration 
Help 
Desk 
by 
email 
at 
<pmbregpend@ctep.nci.nih.gov>. 
 
CTEP Associate Registration Procedures / CTEP-IAM Account 
The Cancer Therapy Evaluation Program (CTEP) Identity and Access Management (IAM) 
application is a web-based application intended for use by both Investigators (i.e., all physicians 
involved in the conduct of NCI-sponsored clinical trials) and Associates (i.e., all staff involved in 
the conduct of NCI-sponsored clinical trials). 
 
Associates will use the CTEP-IAM application to register (both initial registration and annual re-
registration) with CTEP and to obtain a user account. 
 
Investigators will use the CTEP-IAM application to obtain a user account only. (See CTEP 
Investigator Registration Procedures above for information on registering with CTEP as an 
Investigator, which must be completed before a CTEP-IAM account can be requested.) 
 
An active CTEP-IAM user account will be needed to access all CTEP and CTSU (Cancer Trials 
Support Unit) websites and applications, including the CTSU members’ website. 
 
Additional 
information 
can 
be 
found 
on 
the 
CTEP 
website 
at 
<http://ctep.cancer.gov/branches/pmb/associate_registration.htm>. For questions, please contact 
the CTEP Associate Registration Help Desk by email at <ctepreghelp@ctep.nci.nih.gov>. 
 
 
 
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CTSU REGISTRATION PROCEDURES 
This study is supported by the NCI Cancer Trials Support Unit (CTSU).  
 
Requirements for ACCL1034 Site Registration: 
• 
CTSU IRB Certification (for sites not participating via the CIRB) 
• 
CTSU IRB/Regulatory Approval Transmittal Sheet (for sites not participating via the NCI 
CIRB) 
 
Submitting Regulatory Documents: 
Submit completed forms along with a copy of your IRB Approval to the CTSU Regulatory Office, 
where they will be entered and tracked in the CTSU RSS.  
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone: 1-866-651-2878 
Fax: 215-569-0206 
E-mail: CTSURegulatory@ctsu.coccg.org (for regulatory document submission only) 
 
Checking Your Site’s Registration Status: 
Check the status of your site’s registration packets by querying the RSS site registration status page 
of the members’ section of the CTSU website. (Note: Sites will not receive formal notification of 
regulatory approval from the CTSU Regulatory Office.) 
 
Go to https://www.ctsu.org and log in to the members’ area using your CTEP-IAM username 
and password 
 
Click on the Regulatory tab at the top of your screen 
 
Click on the Site Registration tab 
 
Enter your 5-character CTEP Institution Code and click on Go 
 
 
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APPENDIX V: Youth information sheets 
INFORMATION SHEET REGARDING RESEARCH STUDY – ACCL1034 
(for children from 7 through 12 years of age) 
 
A Study of Cleansing Cloths to Prevent Central Line Infections in Children 
 
1. We have been talking with you about your central line. An unwanted problem with central lines is 
that they can get infected and cause an infection in your blood. 
 
2. We are asking you to take part in a research study because you have a central line. A research study 
is when doctors work together to try out new ways to help people who are sick. In this study, we 
are trying to learn more about how to keep central lines from getting infected. We will do this by 
trying a new way to help prevent these infections. 
 
3. Some children in this study will be given a skin cloth that has an ingredient called CHG in it. CHG 
kills germs. Some children will get skin cloths to use that do not have CHG in them, but have other 
ingredients in them to help clean your skin. You have the same chance of getting the CHG cloths 
or the other cloths. You will be asked to use the skin cloths every day. You will be asked to clean 
yourself from the neck down with the cloths instead of or after you have done your normal soap 
and water bathing. You will be asked to use the cloths for 90 days.  
 
4. Sometimes good things can happen to people when they are in a research study. These good things 
are called “benefits.” We hope that a benefit to you of being part of this study is a better chance of 
keeping an infection from happening, if you get the CHG cloths. If you get the other cloths, we 
hope a benefit to you is helping study doctors learn more about how to keep central line infections 
from happening. But, we don’t know for sure if there is any benefit of being part of this study. 
 
5. Sometimes bad things can happen to people when they are in a research study. These bad things 
are called “risks.” The risk to you from this study could be a health problem from the CHG cloths, 
like a rash on your skin. If you get the other cloths, the risks to you is that you many get a rash and 
you may not get a treatment that is better at helping keep central line infections from happening. 
Other things may happen to you that we don’t yet know about. 
 
6. Your family can choose to be part of this study or not. Your family can also decide to stop being 
in this study at any time once you start. There may be other treatments for your illness that your 
doctor can tell you about. Make sure to ask your doctors any questions that you have. 
 
7. We would also like to take a swab of your skin on your neck and in your armpit as part of this 
study. This swab would happen at 3 times during the study – when you start, halfway through the 
study (at 6 weeks), and when you finish the study. We want to see what kind of germs are living 
on your skin and if they are affected by the CHG. If your central line gets infected while you are in 
the study, we would like to test the germs in your blood to see if they are affected by the CHG. We 
will not draw your blood for this study. 
 
8. We will give you a daily calendar to tell us if you used the cleansing cloths each day. We will also 
ask you to tell us if you took a regular bath with soap and water each day and we will ask you about 
the soaps and lotions you use each day. Half-way through the study and at the end of the study, we 
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will ask you to tell us how many cleansing cloths you used. Also at the end of the study, we will 
ask you questions about if you liked the cloths.  
 
9. There is also an optional part of this study that will find out if you have germs on your skin that are 
resistant to germ-killing medications. We also want to find out if the CHG cloths can help keep you 
from getting these germs. For this sub-study, we would like to take swabs from inside your nose 
and your peri-rectum (just outside your rectum) or a stool sample (a sample of feces when you have 
a bowel movement). We would collect these swabs at the same time as the skin swab of your armpit. 
Your family can choose to be a part of this optional sub-study or not.  
 
 
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INFORMATION SHEET REGARDING RESEARCH STUDY – ACCL1034 
(for teens from 13 through 17 years of age) 
 
A Study of Cleansing Cloths to Prevent Central Line Infections in Children and Teens 
 
 
1. We have been talking with you about your central line. An unwanted problem with central lines is 
that they can get infected and cause an infection in your bloodstream. 
 
2. We are asking you to take part in a research study because you have a central line put in for your 
treatment. A research study is when doctors work together to try out new ways to help people who 
are sick. In this study, we are trying to learn more about how to prevent central line infections, in 
children and teens undergoing treatment for cancer. We will do this by trying a new way to prevent 
central line infections. 
  
3. Some children and teens in this study will receive cleansing cloths with CHG in them. CHG is an 
ingredient that kills germs. Others will receive cleansing cloths that do not have CHG in them, but 
have other ingredients to help clean your skin. They are called comfort bath cloths. If you agree to 
be in this study you have a 50-50 chance that you will receive the CHG cloths, and a 50-50 chance 
that you will receive the comfort bath cloths. You will be asked to use the cleansing cloths every 
day. You will be asked to clean yourself from the neck down with the cloths instead of or after you 
have done your usual soap and water bathing. You will be asked to use the cloths for90 days.  
 
4. Sometimes good things can happen to people when they are in a research study. These good things 
are called “benefits.” We hope that a benefit to you of being part of this study is that you will be 
less likely to have a central line infection if you receive the CHG cloths. If you receive the comfort 
bath cloths, we hope a benefit to you is knowing that you will help doctors learn more about how 
to prevent central line infections. But, we don’t know for sure if there is any benefit of being part 
of this study. 
 
5. Sometimes bad things can happen to people when they are in a research study. These bad things 
are called “risks.” If you receive the CHG cloths, the risk to you from this study could be the chance 
of unwanted effects from the CHG such as a skin rash, but this is not very likely. If you receive the 
comfort bath cloths, the risks to you is that you may get a skin rash and you may not receive a 
treatment that is better at helping prevent line infections. Other things may happen to you that we 
don’t yet know about. 
 
6. Your family can choose to be part of this study or not. Your family can also decide to stop being 
in this study at any time once you start. There may be other treatments for your illness that your 
doctor can tell you about. Make sure to ask your doctors any questions that you have.  
 
7. We would also like to take a swab of your skin on your neck and in your underarm as part of this 
study. This swab would happen at 3 times during the study – when you start, halfway through the 
study (at about Day 45), and when you finish the study (at about Day 90). We want to see what 
kind of germs are living on your skin and if they are affected by the CHG. If your central line gets 
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infected while you are in the study, we would like to test the germs in your blood to see if they are 
affected by the CHG. We will not draw your blood for this study.  
 
8. We will give you a daily calendar to tell us if you used the cleansing cloths each day. We will also 
ask you to tell us if you took a regular bath with soap and water each day and we will ask you about 
the soaps and lotions you use each day. Half-way through the study and at the end of the study, we 
will ask you to tell us how many cleansing cloths you used. Also at the end of the study, we will 
ask you questions about if you liked the cloths.  
 
9. There is also an optional part of this study that will find out if you have germs on your skin that are 
resistant to germ-killing medications. We also want to find out if the CHG cloths can help keep you 
from getting these germs. For this sub-study, we would like to take swabs from inside your nose 
and your peri-rectum (just outside your rectum) or a stool sample (collecting a sample of feces 
when you have a bowel movement). We would collect these swabs at the same time as the skin 
swab of your armpit. Your family can choose to be a part of this optional sub-study or not.  
 
 
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21. 
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28. 
Koljalg S, Naaber P, Mikelsaar M: Antibiotic resistance as an indicator of bacterial chlorhexidine 
susceptibility. J Hosp Infect 51:106-13, 2002 
29. 
Maseda H, Hashida Y, Konaka R, et al: Mutational upregulation of a resistance-nodulation-cell 
division-type multidrug efflux pump, SdeAB, upon exposure to a biocide, cetylpyridinium 
chloride, and antibiotic resistance in Serratia marcescens. Antimicrob Agents Chemother 53:5230-
5, 2009 
30. 
Mayer S, Boos M, Beyer A, et al: Distribution of the antiseptic resistance genes qacA, qacB and 
qacC in 497 methicillin-resistant and -susceptible European isolates of Staphylococcus aureus. J 
Antimicrob Chemother 47:896-7, 2001 
31. 
McDonnell G, Russell AD: Antiseptics and disinfectants: activity, action, and resistance. Clin 
Microbiol Rev 12:147-79, 1999 
32. 
Noguchi N, Suwa J, Narui K, et al: Susceptibilities to antiseptic agents and distribution of 
antiseptic-resistance genes qacA/B and smr of methicillin-resistant Staphylococcus aureus isolated 
in Asia during 1998 and 1999. J Med Microbiol 54:557-65, 2005 
33. 
Sheng WH, Wang JT, Lauderdale TL, et al: Epidemiology and susceptibilities of methicillin-
resistant Staphylococcus aureus in Taiwan: emphasis on chlorhexidine susceptibility. Diagn 
Microbiol Infect Dis 63:309-13, 2009 
34. 
Smith K, Gemmell CG, Hunter IS: The association between biocide tolerance and the presence or 
absence of qac genes among hospital-acquired and community-acquired MRSA isolates. J 
Antimicrob Chemother 61:78-84, 2008 
35. 
Tattawasart U, Maillard JY, Furr JR, et al: Development of resistance to chlorhexidine diacetate 
and cetylpyridinium chloride in Pseudomonas stutzeri and changes in antibiotic susceptibility. J 
Hosp Infect 42:219-29, 1999 
36. 
Vali L, Davies SE, Lai LL, et al: Frequency of biocide resistance genes, antibiotic resistance and 
the effect of chlorhexidine exposure on clinical methicillin-resistant Staphylococcus aureus 
isolates. J Antimicrob Chemother 61:524-32, 2008 
37. 
Irizarry L, Merlin T, Rupp J, et al: Reduced susceptibility of methicillin-resistant Staphylococcus 
aureus to cetylpyridinium chloride and chlorhexidine. Chemotherapy 42:248-52, 1996 
38. 
Cookson BD, Bolton MC, Platt JH: Chlorhexidine resistance in methicillin-resistant 
Staphylococcus aureus or just an elevated MIC? An in vitro and in vivo assessment. Antimicrob 
Agents Chemother 35:1997-2002, 1991 
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39. 
Adler A, Yaniv I, Steinberg R, et al: Infectious complications of implantable ports and Hickman 
catheters in paediatric haematology-oncology patients. J Hosp Infect 62:358-65, 2006 
40. 
Simon A, Ammann RA, Bode U, et al: Healthcare-associated infections in pediatric cancer patients: 
results of a prospective surveillance study from university hospitals in Germany and Switzerland. 
BMC Infect Dis 8:70, 2008 
41. 
Bacigalupo A, Ballen K, Rizzo D, et al: Defining the intensity of conditioning regimens: working 
definitions. Biol Blood Marrow Transplant 15:1628-33, 2009 
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SAMPLE INFORMED CONSENT / PARENTAL PERMISSION FOR PARTICIPATION 
IN RESEARCH  
 
 
This model informed consent form has been reviewed by the DCT/NCI and is the official consent 
document for this study. Institutions should use the sections of this document that are in bold type 
in their entirety. Editorial changes to these sections may be made as long as they do not change 
information or intent. If the local IRB insists on making deletions or more substantive modifications 
to any of the sections in bold type, they must be justified in writing by the investigator at the time 
of the institutional audit. 
 
 
RESEARCH INFORMED CONSENT/PARENTAL PERMISSION FORM 
 
ACCL1034, Impact of Cleansing with Chlorhexidine Gluconate (CHG) on Reducing Central Line 
Associated Bloodstream Infection (CLABSI) and Acquisition of Multi-drug Resistant Organisms 
(MDRO) in Children with Cancer or Those Receiving Allogeneic Hematopoietic Cell Transplantation 
(HCT) 
 
 
If you are a parent or legal guardian of a child who may take part in this study, permission from 
you is required. The assent (agreement) of your child may also be required. When we say “you” 
in this consent form, we mean you or your child; “we” means the doctors and other staff. 
 
 
Why am I being invited to take part in this study? 
 
You are being asked to take part in this research study because you about to undergo 
chemotherapy for more than 3 months or you are about to start treatment to prepare for a stem 
cell transplant. You also have a central line, a thin plastic tube placed in a vein in the upper chest 
or neck, which is used for intravenous (IV) medications.  
 
In this study, we want to test if using CHG cleansing cloths can help prevent central line 
associated bloodstream infections (CLA-BSIs). Having a central venous catheter can increase 
the risk of bloodstream infections, CLA-BSIs are often a problem for children and young adults 
undergoing treatment for cancer. CHG stands for chlorhexidine gluconate. This is a special liquid 
cleaner that is used on the skin. CHG is a FDA approved for cleaning the skin before surgery. 
Studies have shown that daily bathing with CHG decreases bloodstream infections in critically ill 
children and adults. Daily bathing with CHG has not been studied in children or adults with cancer 
or those having a stem cell transplant.  
 
This study is called a clinical trial. A clinical trial is a research study involving treatment of a 
disease in human patients. This study is organized by Children’s Oncology Group (COG). COG 
is an international research group that conducts clinical trials for children with cancer. More than 
200 hospitals in North America, Australia, New Zealand, and Europe are members of COG.  
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It is common to enroll children and adolescents with cancer in a clinical trial that seeks to improve 
cancer treatment over time. Clinical trials include only people who choose to take part. You have 
a choice between other treatments to help prevent a central line infection and this clinical trial.  
 
Please take your time to make your decision. You may want to discuss it with your friends and 
family. We encourage parents to include their child in the discussion and decision to the extent 
that the child is able to understand and take part. 
 
 
What is the current standard of treatment for this problem? 
 
Current treatments that are used to help prevent CLA-BSI include: hand washing before the 
central line is placed, having a sterile environment while putting the central line in place, cleaning 
the skin with antimicrobials (germ killing ingredients) such as CHG before the central line is 
placed, and cleaning the skin with CHG with central line dressing changes. Participation in this 
trial would not effect these standard treatments.  
 
 
Why is this study being done? 
 
The overall goal of this study is to compare the effects, good and/or bad, of CHG cloths 
with a control cloth (a cloth without the active ingredient CHG in it) for the prevention of 
CLA-BSI in children and young adults with central lines undergoing treatment for cancer, 
to find out which is better. In this study, you will use either the CHG cloths or the control 
cloths. You will not use both. 
 
Preventing CLA-BSI is important for the following reasons: 
• 
CLA-BSI is one of the most common and serious infections patients get; and 
• 
Many patients with CLA-BSI will need to have their central lines removed and/or replaced. 
 
CHG cloths have been researched in adult patients, and these studies have shown that use of 
CHG, either in cloths or as a liquid wash, helped reduce the chances of getting CLA-BSIs in 
patients with central lines. These studies also showed that the use of CHG reduced the chance 
of a patient acquiring bacteria (germs) resistant to multiple antibiotics. 
 
The use of CHG cloths is experimental in children and adolescents with cancer. Study 
doctors would like to know how effective CHG cloths are for preventing CLA-BSI in children, 
adolescents and young adults undergoing treatment for cancer.  
 
 
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What will happen on this study that is research? 
 
Summary of Study Treatments 
In this study you will get 1 of 2 treatment plans. The 2 treatment plans are the same except for 
the different cleansing cloths you will use. You will not know which treatment you are receiving. 
The treatment on this study will take about 90 days. 
 
The treatment involves the use of CHG cloths or control cleansing cloths in addition to or instead 
of your usual cleansing/bathing. You will be asked to use the cloths once per day, after or instead 
of your usual bathing. Cleansing with the CHG cloths or control cloths will continue for 90 days. 
 
Some soaps and lotions can cause the CHG cloths to not work. You will be asked to only use 
soaps and lotions that work well with CHG regardless of which treatment plan you are receiving. 
A list of compatible soaps and lotions will be provided for you.  
 
The 2 treatment plans are called Arm A and Arm B, as follows: 
 
• Arm A (CHG Cleansing):Subjects will use the study cloth that contains CHG 
  
 
• Arm B (Control Cleansing): Subjects will use the control cloth that does not contain CHG. 
 
 
Random Assignment 
You will receive 1 of 2 different treatment plans. The treatment plan that you receive is decided 
by a process called randomization. Randomization means that the treatment is assigned based 
on chance. It is a lot like flipping a coin, except that it is done by computer. You and your doctor 
will not pick which treatment you get. The randomization process is described in the COG Family 
Handbook for Children with Cancer. 
 
Some subjects will be randomized to use the CHG cloths; others will be randomized to use the 
control cloths. 
 
The cloths look the same. You and your doctor will not know which treatment plan you have been 
assigned to. This information will be kept by the pharmacists at the study coordination site. 
 
Diagram of Treatment 
This chart shows the treatments on this study.  
 
 
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Patient undergoing allogeneic transplant procedure; a non-transplant 
patient with cancer who will be receiving at least 3 months of 
chemotherapy; or a patient receiving less than 3 months of chemotherapy 
followed by a transplant procedure with an eligible central venous 
catheter (CVC) that is planned to be in place for at least 3 months. 
ACCL1034 Enrollment 
Control Cloths 
CHG Cloths 
• 
Baseline skin swab (and swabs for optional study if 
applicable) 
• 
Daily Cleansing for 90 days 
• 
Daily Monitoring for Skin Reactions by medical 
team (or family if outpatient) 
• 
Daily Cleansing Diary by patient or nurse (for 
patients in the hospital) 
Day 90: End of Cleansing. 
• Obtain 3rd skin swab (and swabs for 
optional study if applicable) 
• Obtain  product count  
• Complete the questionnaire. 
Randomization 
to CHG Cloth or 
Control Cloth 
Day 45:  
• Obtain 2nd skin swab(and swabs for optional 
study if applicable) 
• Obtain product count 
Off study 
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Treatment that is Research 
 
Treatment for subjects who are on Arm A (CHG Cloths) 
 
Cloth 
How the treatment will be given  
For How Long 
CHG cloth 
Daily, after (or instead of) your usual 
bathing 
90 days 
 
Treatment for subjects who are on Arm B (Control Cloths) 
 
Cloth 
How the treatment will be given 
For How Long 
Control cloth  
Daily after (or instead of) your usual 
bathing 
90 days 
 
If your chemotherapy treatment changes during the course of this study, as long as you still have 
a central line in place and plan to continue chemotherapy, you may remain on study. 
 
Study Tests and Procedures 
The following tests will be done because you are part of this study. If you were not in the study 
you would probably not have these tests. 
 
1) Skin Swab to Check for Resistance to CHG 
We would like to do some tests to check for the presence of bacteria on your skin. These tests 
are important to help us learn more about CHG cloths and how using them affects the bacteria 
on your skin. These tests will also help us learn more about whether bacteria can develop a 
resistance to CHG. These tests may also help children and young adults who use these cloths in 
the future. The information learned would not change the way you are treated, and the results of 
these tests will not be given to you.  
 
We would take this swab sample at three times: when you enter the study (before treatment has 
started); half-way through the study (about Day 45); and when you finish the study (about Day 
90). We would take this swab sample from the skin on your neck and in your underarm. 
 
2) Testing the Bacteria that Cause Bloodstream Infections 
As part of routine clinical care your blood may be drawn to check to see if you have a bloodstream 
infection. We will not draw your blood for the study. If you have a bloodstream infection while you 
are in the study, we will check to see if the bacteria in your blood are resistant to (or not destroyed 
by) CHG and commonly used antibiotics. You will receive standard clinical treatment for your 
bloodstream infection. 
 
3) Daily Cleansing Diary 
You will be given a daily diary that is like a calendar with checkboxes. You will be asked to mark 
if study cleansing was done each day. We will also ask you to mark if a regular soap and water 
bath was performed each day and we will ask you about any soaps and lotions you used each 
day.  
 
 
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4) Product Count and Satisfaction Questionnaire  
Half way through the study and at the end of your participation in the study, we will ask you to 
count the packets of cleansing cloths you have left. This will give us an idea of how often you 
used the cleansing cloths. The product count should take about 5-10 minutes to complete. 
Additionally, at the end of the study we will ask you to fill out a short survey about the cleansing 
cloths. The survey should take about 5-10 minutes to complete. 
 
Optional Research Study Tests 
We would also like to do some other tests. Some bacteria are able to survive treatment with 
antibiotics. This is called antibiotic resistance. We would like to look for bacteria that are resistant 
to antibiotics. These tests are important to help us learn more about CHG cloths and whether 
using them can help decrease your risk of acquiring bacteria that are resistant to antibiotics.  
 
These tests may also help children and young adults who use these cloths in the future. The 
information learned will not change the way you are treated, and the results of these tests will not 
be given to you. You do not have to do these tests if you do not want to. You can still be in the 
study if you do not want to do these tests. And the end of the consent form, there is a specific 
place to record your decision about taking part in each test.  
 
We would like to collect swab samples from just inside your nose and your peri-rectum (just 
outside your rectum). Instead of a peri-rectum sample, you can choose to provide a stool 
specimen (collecting a sample of your feces when you have a bowel movement). These methods 
of collecting a sample from you will not cause you any pain. The peri-rectum swab (or stool 
sample) and the nose swab would happen when we are obtaining the skin swab.  
 
 
What side effects or risks can I expect from being in the study? 
 
Risks for subjects that receive CHG cloths (study risk) 
Because there is very limited information about how well-tolerated the long-term use 
(more than 1 week) of the CHG cleansing cloths is in children, adolescents, or young adults 
undergoing treatment for cancer, there might be side effects that study doctors can not 
anticipate. The use of CHG cloths instead of control cloths may cause complications. The 
most common risk of using CHG cloths is skin rash or itching of the skin, but rare cases 
of severe allergic reactions, which may be life threatening, have been reported If this 
happens, you will stop using the CHG cloths. No serious allergic reactions were reported 
in recent studies using CHG cloths, including the study of CHG in children in the intensive 
care unit. There were a few skin reactions judged to be related to the CHG. All were mild. 
 
Risks for subjects that receive Control cloths (study risk): 
Subjects that receive the control cloths will be using a cloth without any active medication 
to prevent infections in it. Patients who use the control cloths may also get a mild rash. 
 
 
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In addition to the risks described above, there may be unknown risks, or risks that we did not 
anticipate, associated with being in this study. 
 
 
Are there benefits to taking part in the study? 
 
We hope that this study will help you personally, but we do not know if it will.  
 
A potential benefit to you could include being less likely to have an infection in your blood because 
of a central line infection. 
 
We expect that the information learned from this study will benefit other patients in the future.  
 
 
What other options are there? 
 
Instead of being in this study, you have these options: 
 
• 
Taking part in another study. 
 
Please talk to your doctor about these and other options. 
 
 
How many people will take part in the study? 
 
The total number of people enrolled on this study is expected to be 450.  
 
 
How long is the study? 
 
People in this clinical trial are expected to receive treatment on this study for about 90 days. After 
treatment, you will not have any follow-up examinations or medical tests for this study. 
 
You can stop taking part in the study at any time. However, if you decide to stop participating in 
the study, we encourage you to talk to the study doctor and your regular doctor first. They will 
help you stop safely.  
 
Your doctor or the study doctor may decide to take you off this study: 
• 
if he/she believes that it is in your best interest; 
• 
if your disease comes back during treatment; 
• 
if you experience side effects from the treatment that are considered too severe; or 
• 
if new information becomes available that shows that another treatment would be better for 
you. 
 
 
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What about privacy? 
 
We will do our best to make sure that the personal information in your medical record will be kept 
private. However, we cannot guarantee total privacy. Your personal information may be given out 
if required by law. If information from this study is published or presented at scientific meetings, 
your name and other personal information will not be used. 
 
The Children’s Oncology Group has received a Certificate of Confidentiality from the federal 
government, which will help us protect the privacy of our research subjects. Information about the 
certificate is included in Attachment #1. 
 
Organizations that may look at and/or copy your research or medical records for research, quality 
assurance and data analysis include groups such as: 
 
• Children's Oncology Group 
• 
Representatives of the National Cancer Institute (NCI), Food and Drug Administration 
(FDA), and other U.S. and international governmental regulatory agencies involved in 
overseeing research 
• The Institutional Review Board of this hospital 
• Pediatric Central Institutional Review Board (CIRB) of the National Cancer Institute 
• Seattle Children’s Hospital 
 
 
What are the costs? 
 
Taking part in this study may lead to added costs to you or your insurance company. There are 
no plans for the study to pay for medical treatment. Please ask about any expected added costs 
or insurance problems. Staff will be able to assist you with this. 
 
The study bathing cloths are being provided at no charge to you. Neither you nor your insurance 
company will be charged for the study bathing cloths. 
 
In the case of injury or illness resulting from this study, emergency medical treatment is available 
but will be provided at the usual charge. No funds have been set aside to compensate you in the 
event of injury. However by signing this form, you are not giving up any legal rights to seek to 
obtain compensation for injury. 
 
You or your insurance company will be charged for continuing medical care and/or hospitalization.  
 
 
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Funding support 
 
If you choose to enroll on this study, this institution will receive some money from the Children’s 
Oncology Group to do the research. There are no plans to pay you for taking part in this study. 
 
This study includes providing specimens to the researcher. There are no plans for you to profit 
from any new product developed from research done on your specimens.  
 
 
What are my rights as a participant? 
 
Taking part in this study is voluntary. You may choose not to be in this study. If you decide not to 
be in this study, you will not be penalized and you will not lose any benefits to which you are 
entitled. You will still receive medical care.  
 
You can decide to stop being in the study at any time. Leaving the study will not result in any 
penalty or loss of benefits to which you are entitled. Your doctor will still take care of you. 
 
We will tell you about new information that may affect your health, welfare, or willingness to stay 
in this study. A committee outside of COG closely monitors study reports and notifies COG if 
changes must be made to the study. Members of COG meet twice a year to discuss results of 
treatment and to plan new treatments.  
 
During your follow-up visits after treatment, you may ask to be given a summary of the study 
results after they are written up. This may be several years from now since all people on the study 
need to have completed treatment.  
 
 
Whom do I call if I have questions or problems? 
 
For questions about the study or if you have a research related problem or if you think you have 
been injured in this study, you may contact Dr. XXXX or your doctor at XXXX. 
 
If you have any questions about your rights as a research participant or any problems that you 
feel you cannot discuss with the investigators, you may call XXXX IRB Administrator at XXXX. 
 
If you have any questions or concerns that you feel you would like to discuss with someone who 
is not on the research team, you may also call the Patient Advocate at XXXX. 
 
 
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Where can I get more information? 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This Web site 
will not include information that can identify you. At most, the Web site will include a summary of 
study results. You can search this Web site at any time. 
 
The COG Family Handbook for Children with Cancer has information about specific cancers, 
tests, treatment side effects and their management, adjusting to cancer, and resources. Your 
doctor can get you this Handbook, or you can get it at www.curesearch.org/. 
 
Visit the NCI's Web site at http://www.cancer.gov. 
 
If you are in the United States, you may call the NCI's Cancer Information Service at: 
1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615.  
 
Information about long term follow-up after cancer treatment can be found at: 
http://www.survivorshipguidelines.org/. 
 
You will get a copy of this form. You may also ask for a copy of the protocol (full study plan). 
 
 
Specimens for optional research tests 
 
The choice to let us use specimens for research is up to you. No matter what you decide to do, it 
will not affect your care. You can still be a part of the main study even if you say ‘No’ to taking 
part in any of these optional research studies. 
 
If you decide now that your specimens can be used for research, you can change your mind at 
any time. Just contact us and let us know that you do not want us to use your specimens. Then, 
any specimens that we have will be destroyed.  
 
Please read the information below and think about your choices. After making your decisions, 
check “Yes” or “No”, then add your initials and the date after your answer. If you have any 
questions, please talk to your doctor or nurse, or call our research review board at the IRB’s phone 
number included in this consent. 
 
#1 
Swabs of my nose and peri-rectum or stool may be sent to a laboratory and studied to see 
if special tests can identify germs on my skin and if they have developed a resistance to 
germ-killing substances. 
 
Yes_____  
No_____  
________ / _______ 
 Initials  
Date 
 
 
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Signature 
 
I have been given a copy of all _____ pages of this form. The form includes one (1) 
attachment. 
 
I have reviewed the information and have had my questions answered.  
I agree to take part in this study. 
 
Participant 
Date  
 
 
Parent/Guardian 
Date  
 
 
Parent/Guardian 
Date  
 
 
Physician/PNP obtaining consent 
Date  
 
 
IRB# _______________ 
IRB Approved: ___________ 
 
 
 
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Attachment #1 
 
Certificate of Confidentiality 
 
The Children's Oncology Group has received a Certificate of Confidentiality from the federal 
government, which will help us protect the privacy of our research subjects. The Certificate 
protects against the involuntary release of information about subjects collected during the course 
of our covered studies. The researchers involved in the studies cannot be forced to disclose the 
identity or any information collected in the study in any legal proceedings at the federal, state, or 
local level, regardless of whether they are criminal, administrative, or legislative proceedings. 
However, the subject or the researcher may choose to voluntarily disclose the protected 
information under certain circumstances. For example, if the subject or his/her guardian requests 
the release of information in writing, the Certificate does not protect against that voluntary 
disclosure. Furthermore, federal agencies may review our records under limited circumstances, 
such as a DHHS request for information for an audit or program evaluation or an FDA request 
under the Food, Drug and Cosmetics Act. The Certificate of Confidentiality will not protect against 
the required reporting by hospital staff of information on suspected child abuse, reportable 
communicable diseases, and/or possible threat of harm to self or others. 
 
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