Computerized Cognitive Training for Pediatric Brain Tumor Patients: A Pilot Study
Phase: NA
Conditions: Brain Neoplasm, Recurrent Brain Neoplasm
Sponsor: Children's Oncology Group

      ACCL10P1 
 
Activated: November 4, 2013      
Version Date: 08/06/2018 
Closed: March 30, 2023 
Amendment #: 2 
 
 
 
CHILDREN'S ONCOLOGY GROUP 
 
 
ACCL10P1 
 
Computerized Cognitive Training for Pediatric Brain Tumor Patients: A Pilot Study 
 
A COG Groupwide Study 
 
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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

      ACCL10P1 
 
Version Date: 08/06/2018 
 
 
 
 
 
 
Page 2 
TABLE OF CONTENTS 
SECTION 
PAGE 
STUDY COMMITTEE 
3 
ABSTRACT 
5 
EXPERIMENTAL DESIGN SCHEMA 
6 
1.0 
SPECIFIC AIMS 
7 
1.1 
Primary Objective 
7 
1.2 
Exploratory Objective 
7 
2.0 
BACKGROUND AND RATIONALE 
7 
2.1 
Brain Tumors in Children and Adolescents – Acute and Long-Term Effects of Treatment 
8 
2.2 
Existing Efforts to Prevent or Improve Neurocognitive Late Effects 
8 
2.3 
Cognitive Training Programs 
10 
2.4 
Summary 
12 
3.0 
ENROLLMENT PROCEDURES AND ELIGIBILITY CRITERIA 
13 
3.1 
Study Enrollment 
13 
3.2 
Patient Eligibility Criteria 
15 
4.0 
TREATMENT PLAN 
16 
4.1 
Overview of Treatment Plan 
16 
4.2 
Criteria for Randomization 
17 
4.3 
Procedures 
17 
4.4 
Computerized Cognitive Training Treatment 
18 
4.5 
Neuropsychological and Behavioral Measures 
19 
4.6 
Feasibility Interview 
20 
4.7 
Testing Schedule 
20 
4.8 
Feedback to Participants 
21 
5.0 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA 21 
5.1 
Criteria for Removal from Protocol Therapy 
21 
5.2 
Off Study Criteria 
21 
6.0 
STATISTICAL CONSIDERATIONS 
21 
6.1 
Statistical Design 
21 
6.2 
Patient Accrual and Expected Duration of Trial 
22 
6.3 
Statistical Analysis Methods 
22 
6.4 
Gender and Minority Accrual Estimates 
24 
7.0 
RECORDS AND REPORTING 
24 
7.1 
CDUS 
24 
REFERENCES 
25 
APPENDIX I: CTEP AND CTSU REGISTRATION PROCEDURES 
28 
APPENDIX II: COGMED RM AND COGMED JM 
30 
APPENDIX III: STUDY ASSESSMENT INSTRUMENTS 
31 
APPENDIX IV: SOCIOECONOMIC STATUS MEASURE 
34 
APPENDIX VA: PARENT FEASIBILITY AND ACCEPTABILITY INTERVIEW 
36 
APPENDIX VB: CHILD FEASIBILITY AND ACCEPTABILITY INTERVIEW 
39 
APPENDIX VI: COMPUTER USE QUESTIONNAIRE 
40 
APPENDIX VII: YOUTH INFORMATION SHEETS 
41 
 
 

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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 
 
Pediatric patients with brain tumors receiving cranial radiation therapy (CRT) have an increased likelihood of 
experiencing significant neurocognitive decline over time, especially with regard to working memory (WM) 
and attention skills. These deficits, in turn, are associated with declines in intelligence quotient (IQ) and 
academic performance, which can impair quality of life (QOL) of survivors into adulthood. Thus, there is a 
critical need to develop methods to preserve neurocognitive functioning in those at risk. Computerized 
cognitive training (CT) is a convenient and cost-effective way of potentially preserving brain function in 
patients with brain tumors. To date, however, no studies have examined the feasibility or efficacy of this type 
of intervention in children receiving CRT. There are no known adverse effects of the intervention; rather, 
children find it an enjoyable and stimulating experience that can be completed at home. Computerized CT is a 
method that, if established as feasible and efficacious, has high potential for rapid translation to clinical practice.  
 
 
 
 
 
 
 
 

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EXPERIMENTAL DESIGN SCHEMA  
 
 
 
* See Section 3.2 for Eligibility Criteria.  
** See Section 4.5 and Appendix III for required and optional (but highly encouraged) study assessments. 
Timing required: Baseline Testing and Randomization within 2-4 months after completion of CRT. 
# Cognitive Training must initiate within 2 weeks after Baseline Testing (see Section 3.1.4). Patients 
with progressive disease or relapse will be removed off protocol therapy. 
@ Randomization is via Callback: see Section 3.1.6 for procedure summary and Section 4.2 for criteria. 
Study Enrollment 
& Coach Assignment 
Within 2-4 months after 
completion of  
Cranial Radiation Therapy 
Patient Identification 
For Eligibility* 
Cranial Radiation 
Therapy 
Randomization@ 
(N=60) 
Arm A 
Adaptive Program** 
Arm B 
Non-Adaptive Program** 
Within 3 weeks of 
training completion 
6 (±1) months after 
training completion 
Post-Intervention 
Testing**# 
Follow-Up 
Testing**# 
Study Completion 
Cognitive Training# 
25 training sessions 
over 5-9 weeks  
Baseline Testing** 
Patient Does Not 
Meet Criteria for 
Randomization 
Off 
Study 

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1.0 
SPECIFIC AIMS 
 
1.1 
Primary Objective 
To assess the feasibility of a home-based, computerized cognitive training program for 
patients with pediatric brain tumors who are undergoing cranial radiation therapy (CRT), 
treated in COG institutions. 
 
Hypothesis: The home-based computerized cognitive training (CT) program will be feasible 
and acceptable, as defined by 75% of randomized participants across sites achieving 80% 
treatment compliance, and parent- and child- reported technical ease-of-use and satisfaction. 
 
1.2 
Exploratory Objective 
To estimate the effect size of this program on measures of attention and working memory 
in patients with brain tumors treated with CRT in order to design a definitive large-scale 
clinical trial. 
 
Hypothesis: Participants will show increases in attention and working memory compared 
to participants in the active control group, as measured by both objective and subjective 
measures of attention and working memory following completion of the intervention. 
Moreover, participants will maintain increased attention and working memory scores at a 
6-month follow-up assessment. 
 
 
2.0 
BACKGROUND AND RATIONALE 
 
The majority of children with brain tumors who receive CRT will experience neurocognitive 
deficits. In particular, deficits in attention and working memory have emerged as among the most 
common neurocognitive sequelae of CRT. These difficulties make it harder for children to process 
and store new information, and contribute to declines in IQ and academic functioning over time. 
Later, these effects, and others, lead to limited vocational opportunities and reduced likelihood of 
independent living. As such, there is a critical need for interventions to mitigate deficits and/or 
restore cognitive functioning in this population.  
 
Home-based computerized cognitive training (CT) is a novel approach that has shown robust 
efficacy in improving working memory in children with attention disorders and localized brain 
injury. Our research team is currently evaluating the feasibility and efficacy of such an intervention 
delivered to survivors of pediatric cancer with neurocognitive late effects. However, the potential 
for these interventions to preserve cognitive functioning in children receiving CRT has never been 
evaluated.  
 
Using a randomized clinical trial design conducted in multiple, COG-affiliated institutions, the 
overarching goal of this proposal is to evaluate whether a home-based computerized CT 
intervention is feasible for use with pediatric brain tumor patients during the active phase of 
treatment. Potentially, preservation of working memory (WM) skills in children during the period 
following radiation exposure may allow for long-term preservation of brain function. 
Consequently, changes that that are thought to stem from weak WM, such as declining intellectual 
and academic functioning, may also be averted. The results of this study will serve as pilot data on 
the basis of which a larger, randomized clinical trial will be planned.  
 

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2.1 
Brain Tumors in Children and Adolescents – Acute and Long-Term Effects of Treatment 
Brain tumors are often treated with some 
combination of neurosurgery, chemotherapy 
and CRT. While advances in treatment 
have increased the likelihood of cure, 
survival 
is 
often 
characterized 
by 
significant impairments in neurocognitive 
functioning, including academic failure, 
deficits 
in 
social 
functioning, 
and 
vocational difficulty.3,4 Identified risk 
factors include age under 6 to 8 years at 
diagnosis, female sex, tumor location, 
shunted 
hydrocephalus, 
presence 
of 
seizures, post-operative sequelae such as 
stroke, infection or cerebellar mutism, and 
importantly, use of CRT.5 To mitigate 
these 
impairments, 
researchers 
have 
adjusted treatment protocols to eliminate or 
delay CRT, and to reduce radiation doses 
and fields. These measures, along with 
improved neurosurgical techniques, have 
reduced 
treatment-related 
cognitive 
declines while maintaining or improving survival rates.6 Despite these advances, however, 
recent studies have found that 40 to 100% of brain tumor survivors evidence some 
cognitive deficit resulting from disease and/or treatment effects.7,8 Decreases in IQ of more 
than one standard deviation are common, particularly for children treated at younger ages.2 
Declines in nonverbal and full-scale scores tend to be more precipitous than changes in 
verbal IQ (see Figure 1). 
 
Notably, investigators have posited that attention and WM deficits underlie the changes in 
intelligence and academic performance frequently seen in survivors of brain tumors.9-12 In 
healthy children, Fry and Hale13 found that almost half of developmental increases in IQ 
could be attributed to age-related improvements in WM and processing speed. Similar 
findings have been documented in pediatric cancer survivors. Schatz and colleagues, for 
example, found that 45 percent of the variance in IQ was attributable to these processes14. 
In addition, Reddick and colleagues found that 70 percent of survivors’ functional 
impairments at school and other settings were accounted for by their attention problems11.  
 
Because WM capacity increases 2- to 3- fold from ages 4 to 16,15 disruption to the 
development of these processes can significantly curtail a wide range of a child’s abilities 
over time. This may take the form of declines in IQ, as described above, or difficulty with 
executive functioning and academic performance. For example, children with reading 
difficulties frequently have deficits in WM which appear to contribute to problems with 
phonological memory.16,17 Math skills are also strongly linked to WM capacity in typically-
developing children, accounting for between 20% - 57% of the variance in math 
performance.16,18,19 Thus, improving or preserving WM in these patients may help to offset 
declines in IQ, executive functioning, and academic performance over time.  
 
2.2 
Existing Efforts to Prevent or Improve Neurocognitive Late Effects 
Given the severity of neurocognitive late effects experienced by many survivors of 
pediatric brain tumors, investigators over the last decade have focused on methods of 
 
Figure 1: Estimated declines in IQ in pediatric brain 
tumor survivors following CRT 2 

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preventing or ameliorating late effects. Improvements in surgical techniques, conformal 
radiation therapy, and radiation dose reductions have been partially successful in reducing 
toxicity;6,20 however, neurocognitive sequelae remain prevalent.21 Beyond changes in 
primary therapy, based on evidence of attention and WM deficits, researchers also have 
started to investigate the efficacy of interventions targeting these impairments. These 
efforts have historically focused on compensation for acquired deficits rather than 
restoration of functioning. Indeed, the current standard-of-care for survivors with cognitive 
and academic late-effects emphasizes school-based accommodations such as preferential 
seating and extended time for coursework and exams.22 
 
More recent interventions including pharmacotherapy and cognitive remediation have been 
tested in pediatric cancer survivors. The psychostimulant methylphenidate has improved 
performance on attention and learning tasks in both adult brain tumor patients23 and 
survivors of childhood cancer,24-26 though most cognitive and academic scores remained 
unchanged in children. Cognitive remediation27,28 and problem-solving29 for pediatric 
cancer survivors with impairment also have been explored. The most rigorously-evaluated 
program focused on the acquisition of strategies to improve cognitive, attentional, and 
academic performance; it consisted of two-hour, therapist-directed sessions every week for 
six months. While this program has shown improvement in academic performance of some 
survivors,28 effect sizes for many indices of academic and adaptive functioning were small. 
Moreover, only 60% completed the program; it may be that the frequency and duration of 
clinic visits were not feasible for some subjects.30 Short-term, focused interventions that 
can be delivered outside of a clinic setting may enhance feasibility for this population.  
 
Compared with the growing empirical basis for intervening during the survivorship period, 
there are almost no studies that have attempted to intervene during the treatment phase, 
before neurocognitive declines occur. Yet, preliminary data from research on traumatic 
brain injuries31 and 22q11 deletion syndrome32 indicate that there may be a therapeutic 
window of opportunity following primary brain injury in which to attenuate secondary or 
delayed morbidity. Under this assumption, one recent, as yet unpublished, study used an 
intense (40-50 hrs) program focused on improving math concepts, including problem 
solving, with a small sample of children newly diagnosed with leukemia.33 Compared to 
children who did not receive the intervention, those who did improved their math 
achievement by greater than one standard deviation. Importantly, they also evidenced 
improvements in their nonverbal WM scores, which were not targeted by the intervention. 
In contrast, nonverbal WM scores in the control group declined over the intervention and 
follow-up period. Although preliminary, these data suggest the possibility that early 
intervention can prevent neurocognitive decline in children who are receiving treatment 
for childhood cancer. As with cognitive remediation efforts in the survivorship period, 
however, such an intense program may be impractical for, or unavailable to, a sizable 
portion of patients and their families.  
 
In sum, although rehabilitative strategies exist, none has been shown to be robustly 
effective in restoring functioning once late effects have developed. The optimal strategy to 
maximize cognitive functioning is to prevent these deficits from occurring. Therefore, there 
is a critical need for programs targeting the preservation of neurocognitive functioning in 
pediatric patients with brain tumors being treated with CRT. Ideally, such an intervention 
should be effective, short-term and applicable to a wide-range of potential participants, who 
will not be limited by time, distance or cost. The current application addresses this need. 
 

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2.3 
Cognitive Training Programs 
CT programs have been used for decades to reduce or stabilize neurocognitive deficits in 
populations of individuals with accidental or disease-related brain injury. These activities 
can include paper-and-pencil tasks, memory games, and one-on-one instruction with a 
cognitive “coach,” usually a neuropsychologist, occupational therapist, educator, or similar 
professional. Many computerized CT programs targeting attention and WM problems, 
primarily in children and adolescents with attention deficit hyperactivity disorder (ADHD), 
have recently been developed. Most consist of a series of tasks of increasing complexity, 
and there is emerging support for their efficacy.34-39  
 
2.3.1 
Cogmed 
Recently, Klingberg and colleagues developed a computerized CT program 
targeted at reducing deficits in WM.35,36 The program, called Cogmed RM, consists 
of game-like exercises targeting visuo-spatial WM skills. Feedback about 
participants’ performance is given visually and verbally to increase interest and 
compliance. The program is adaptive, such that difficulty of the training tasks 
increases with the skill of the participant on a trial-by-trial basis. The program is 
designed primarily for home use, with minimal training and support required. Its 
use has increased WM functioning in a wide range of samples, including healthy 
adults, stroke patients, children with specific WM deficits, and children with 
ADHD.35,36,38-43 WM skill has improved by both objective and subjective 
report,35,39 there have been associated brain changes captured by functional 
imaging,40 and, importantly, improvements in academic functioning.38 Effect sizes 
for most outcome measures were medium to large, and broadly consistent with 
those obtained from many medication trials for patients with ADHD.  
 
2.3.2 
Preliminary Data  
Dr. Hardy has thus far performed two separate, small-sample trials of 
computerized CT with survivors of childhood cancer who have received CNS-
impacting treatment (i.e., acute lymphoblastic leukemia (ALL) and brain tumors). 
The first trial, funded by Duke’s Comprehensive Cancer Center, evaluated the 
efficacy of a computerized CT program known as Captain’s Log with nine 
survivors of pediatric cancer.1 The program was associated with good feasibility 
and acceptability, and outcomes reflected significant improvements in WM and 
parent-rated inattention symptoms over a 3-month trial (see Figure 2). However, 
the study was limited by the lack of a control group and very small sample size. 

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The second trial, Targeting Inattention in Childhood Cancer Survivors (TRICCS; 
NCI R03-CA132570), addressed several of the limitations of the first, using the 
Cogmed RM program (described above). Cogmed was selected for the second trial 
given its focus on improving WM skills and on the number of published studies 
indicating its efficacy with ADHD and other samples. The trial included both an 
intervention group that completed an adaptive version of the program and an active 
control group. Compliance rates for the trial (n = 20) were high (Mean = 98.1% of 
sessions completed, SD = 6.02). Feasibility and acceptability indicate high levels 
of participant and parental satisfaction with the intervention. Indeed, 94.4% of 
parents reported that they were somewhat or very satisfied with their child’s 
participation in the intervention, and 68.7% of children indicated that they either 
often or always enjoyed their training sessions. Further, data from the Cogmed 
Training Index, a program-specific score that is used to gauge children’s progress 
with WM skills targeted by the Cogmed tasks, indicated that the participants 
achieved a mean training index improvement of 31 (SD = 11, range = 15 – 54), 
very similar to that of a sample of 550 children with ADHD who have completed 
the program with a mean index improvement of 26.2.44 Finally, survivors 
completing the adaptive version evidenced increases in attention (d = .52) and WM 
(d = .46; as measured by the Wide Range Assessment of Memory and Learning – 
Second Edition45) and decreases in parent-rated attention problems (d = .50; as 
measured by the Conners-3 Parent Rating Scale46) as compared to survivors 
completing the non-adaptive version (Fig. 3).47  
 
Figure 2: Changes in parent-rated attention problems over the course of a computerized cognitive intervention 
for survivors of ALL and brain tumors 1 

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2.4 
Summary 
The current standard of care is to address survivors’ neurocognitive difficulties after they 
appear, either via pharmacological intervention or cognitive remediation, resulting in 
modest improvements at best. Thus, there is a critical need for novel and efficacious 
treatment approaches targeted towards mitigating CRT-associated difficulties in this 
population. Computerized CT has no known adverse effects, will not interact with 
pharmacological interventions, is cost-effective, and can be easily administered in the 
home setting with parental oversight. If such a program is shown to be feasible and 
efficacious in a sample of pediatric patients at high risk for neurocognitive deficits, the 
intervention could be rapidly translated to clinical practice.  
 
 
 
 
Figure 3: Pre-post change scores on outcome measures for pediatric ALL and brain 
tumor survivors completing adaptive vs. non-adaptive versions of Cogmed. 

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3.0 
ENROLLMENT PROCEDURES AND ELIGIBILITY CRITERIA 
 
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 Patient Registry module in OPEN 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. For additional help or information, please contact the CTSU Help 
Desk at 1-888-823-5923 or ctsucontact@westat.com. 
 
In order for an institution to maintain COG membership requirements, every patient 
with a known or suspected neoplasm needs to be offered participation in APEC14B1, 
Project:EveryChild A Registry, Eligibility Screening, Biology and Outcome Study. 
  
Please see Appendix I 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 
Each investigator or group of investigators at a clinical site must obtain IRB 
approval for this protocol and submit IRB approval and supporting documentation 
to the CTSU Regulatory Office before they can be approved to enroll patients. 
Assignment of site registration status in the CTSU Regulatory Support System 
(RSS) uses extensive data to make a determination of whether a site has fulfilled 
all regulatory criteria including but not limited to the following: 
• 
An active Federal Wide Assurance (FWA) number 
• 
An active roster affiliation with the Lead Network or a participating 
organization 
• 
A valid IRB approval 
• 
Compliance with all protocol specific requirements. 
 
In addition, the site-protocol Principal Investigator (PI) must meet the following 
criteria: 
• 
Active registration status 
• 
The IRB number of the site IRB of record listed on their Form FDA 1572 
• 
An active status on a participating roster at the registering site. 
 
For information about the submission of IRB/REB approval documents and other 
regulatory documents as well as checking the status of study center registration 
packets, please see Appendix I.  
 
Institutions with patients waiting that are unable to use the Portal should alert the 
CTSU Regulatory Office immediately at 1-866-651-2878 in order to receive 
further instruction and support. For general (non-regulatory) questions call the 
CTSU General Helpdesk at: 1-888-823-5923. 

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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. For sites using the CIRB, IRB approval information is 
received from the CIRB and applied to the RSS in an automated process. Signatory 
Institutions must submit a Study Specific Worksheet for Local Context (SSW) to 
the CIRB via IRBManager to indicate their intent to open the study locally.  The 
CIRB’s approval of the SSW is then communicated to the CTSU Regulatory 
Office.  In order for the SSW approval to be processed, the Signatory Institution 
must inform the CTSU which CIRB-approved institutions aligned with the 
Signatory Institution are participating in 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 
Patients may be enrolled on the study once all eligibility requirements for the study 
have been met. Study enrollment is accomplished by going to the Enrollment 
application in eRDES. If you have problems with enrollment, refer to online help 
in the Applications area of the COG Website.  
 
3.1.4 
Timing 
Patients must be enrolled in the study via eRDES prior to baseline testing. After 
baseline testing, patients meeting criteria for randomization (per Section 4.2) will 
be randomized prior to starting cognitive training sessions. Baseline testing 
followed by randomization must both occur within 2-4 months after completion 
of CRT. Cognitive training sessions must be initiated within 2 weeks after 
completion of baseline testing.  
 
3.1.5 
Inclusion of Women and Minorities 
Both males and females of all races and ethnic groups are eligible for this study.  
 
3.1.6 
Randomization 
After baseline testing and within 2-4 months of completing CRT, patients meeting 
criteria for randomization (see Section 4.2) will be assigned to either 
Arm A (adaptive testing) or Arm B (non-adaptive testing). Randomization will be 
stratified by age (< 8 vs. ≥ 8 years), treatment intensity (whole brain vs. focal 
radiation) and Coach (A vs. B). Note: the patient’s coach assignment can be found 
on the Eligibility form receipt in eRDES (the field is auto-populated by the system 
after the form has been validated and saved). Coach A or B assignment at enrollment 
should not be confused with the assignment to treatment Arm A or B at randomization.  
 
Treatment randomization is accomplished by completing the Callback in eRDES 
(refer to instruction on the Case Report Forms for details). The Callback must be 
completed prior to initiation of study treatment.  
 
 

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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.  
 
INCLUSION CRITERIA 
3.2.1 
Age 
The patient must be aged 6 to 16 years at study enrollment, inclusive. 
 
3.2.2 
Diagnosis and Treatment 
Patient must be newly diagnosed or relapsed/progressed with a brain tumor that 
has not previously been treated with CRT.  
Note: COG therapeutic study participation is not required for ACCL10P1 enrollment. 
 
3.2.3 
Timing 
Patient enrollment must occur within 4 calendar months following completion of CRT.  
Reminder: after patient enrollment, baseline testing followed by randomization 
must occur within 2-4 months after completion of CRT (see Section 3.1.4). 
 
3.2.4 
Training Support 
3.2.4.1 The patient must have an identified caregiver who is willing and able to 
oversee the training practice during the intervention period (i.e., for 
5-9 weeks starting approximately 3 months after completion of CRT). 
3.2.4.2 The patient must have access to a telephone and phone number where they 
can be reached. 
 
3.2.5 
Language Skills 
The patient and caregiver must have reading, speaking and listening comprehension 
of English. 
 
EXCLUSION CRITERIA 
3.2.6 
Diagnosis and Treatment 
3.2.6.1 Patients with pontine glioma are not eligible.  
3.2.6.2 Patients with an estimated survival of less than one year are not eligible. 
3.2.6.3 Patients with a history of traumatic brain injury prior to tumor diagnosis 
are not eligible. 
 
3.2.7 
Performance Level 
3.2.7.1 Patients with a motor, visual, or auditory handicap that prevents computer 
use (e.g., unresolved posterior fossa syndrome) are not eligible to 
participate in this trial. 
3.2.7.2 Patients with Full-Scale IQ < 70 per previous testing OR existing 
diagnosis of/educational classification as a student with an Intellectual 
Disability are not eligible. 

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REGULATORY 
3.2.8 
All patients and/or their parents or legal guardians must sign a written informed 
consent (patient assent is also recommended when applicable according to each 
institution’s policy). 
3.2.9 
All institutional, FDA, and NCI requirements for human studies must be met. 
 
 
4.0 
TREATMENT PLAN 
 
4.1 
Overview of Treatment Plan 
Our goal is to establish feasibility and preliminary efficacy of this intervention in a small 
sample of 60 randomized participants. Patients 6-16 years old newly diagnosed with a brain 
tumor requiring CRT will be identified for participation in this study by the institutional 
oncologist, nurses, psychologist, or other member of the healthcare team at each participating 
site. This age range was selected because it includes children who are old enough to be able 
to complete the intervention, and young enough to be at substantial risk for CRT-related 
late effects.2,5,7,8,48 
 
Within 2-4 months of completing CRT, enrolled participants will complete baseline 
measures (see Section 4.7 and Appendix III). Those who meet criteria for randomization per 
Section 4.2 will be randomized to the intervention arm or an active control group. Almost all 
participants are expected to be receiving chemotherapy during this period. Randomization 
will be stratified by known risk factors including age (< 8 vs. ≥ 8),5 treatment intensity (whole 
brain vs. focal radiation) and also by Coach (A versus B).2,48 Reminder: at enrollment 
participants will be randomized to receive Cogmed coaching from one of two coaches (Coach 
A or Coach B) according to a block randomization schedule. The patient’s coach assignment 
record can be found on the Eligibility form receipt in eRDES (a field auto-populated by the 
system after the form has been validated and saved). 
 
The design will be a single-blind, dose-controlled trial in which half of the participants will 
be randomized to the adaptive intervention condition and half will complete training on a 
non-adaptive comparison computer program. At each assessment (baseline, post-treatment, 
and follow-up), the person performing any cognitive testing (i.e., computerized assessment 
and/or the optional psychologist battery) will be blinded to randomization. Given the role 
of cognitive-behavioral coaching in the CT program, it will not be possible for coaches to 
be blinded to participants’ randomization status, but coaches will not perform any of the 
pre- or post-training assessments. In our previous work, we had no difficulty maintaining 
this blind between coaches and examiners. Parents and participants will be blinded to 
randomization, at least initially. Because they will have been informed that the two study 
conditions are distinguished by their difficulty level, some parents and/or children may be 
able to guess their randomization status. Reminder: if patient starts or changes dosage of 
psychostimulant medications during the study period, patient will be removed off study. 
 
Cogmed (see Appendix II) is a home-based, computerized, interactive, audio-visual CT 
program. Designed to be completed over 25 training sessions spanning 5-9 weeks, Cogmed 
consists of twelve engaging exercises that target skills involving visuo-spatial and verbal WM 
(separate versions of the program are available for preschool- and school-aged children). This 
CT program is particularly appropriate for the pediatric brain tumor population because of its 
ease-of-use, ability to be completed at home, and established efficacy in other patient 

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populations.35,38,41,42 Primary outcomes will include measures of attention and WM. Of note, 
participants assigned to the non-adaptive condition will complete a modified version of the 
computerized CT consisting of tasks that never increase in difficulty. If patients do not complete 
the training within 9 weeks, they will be removed off protocol therapy (see Section 5.1).  
 
Participants will be asked to return to the clinic within three weeks of completing the 
intervention program for brief follow-up testing; ideally this appointment would be 
scheduled in conjunction with one of their regular clinic visits. Six months following 
completion of the intervention patients will return to complete another brief assessment to 
evaluate stability of any changes over time. At that time, following completion of all testing 
procedures, families will be informed of whether they received the adaptive or non-
adaptive intervention (i.e., participants will be unblinded) and families enrolled in the non-
adaptive arm of the study will be given the opportunity to complete the adaptive training 
at no cost and with the support of a Cogmed-certified coach. 
 
4.2 
Criteria for Randomization 
Patients must fulfill all criteria listed below to proceed to randomization, otherwise, 
patient will be off study. 
 
4.2.1 
Timing 
The maximum period between the end of radiation and randomization is 4 months.  
 
4.2.2 
Criteria 
4.2.2.1 Patients with evidence of IQ < 70 (from psychologist administered baseline 
testing or other cognitive testing) OR existing diagnosis of/educational 
classification as a student with an Intellectual Disability, will not be eligible. 
 
4.2.2.2 Patients diagnosed with any mental health disorder (e.g., depression, 
anxiety, oppositional defiant disorder) that, in the treating physician or 
psychologist’s opinion, would preclude or take treatment precedence over 
participation in CT will not be eligible.  
 
Reminder: if a patient starts or changes dosage of a psychostimulant medications, 
the patient will be taken off study – See Section 5.2. 
 
4.3 
Procedures  
Three study visits will be required for participation in the study (see Section 4.7). First is 
the screening/baseline assessment, which will be conducted for all participants following 
study enrollment. The baseline testing must be performed within 4 months after the 
completion of CRT. The two remaining study visits are the post-intervention assessment 
and the follow-up assessment, which will be needed only for participants who meet criteria 
for randomization and who are randomized. Screening/baseline assessment may include 
administration of an abbreviated intellectual test battery, a WM battery, and a computerized 
attention measure (see Appendix III). Parents will complete questionnaire measures 
regarding their child’s adaptive, behavioral, emotional, and attentional functioning. Clinical 
interviewing will be conducted to clarify any potential problems identified on the 
questionnaires; final decisions about psychosocial eligibility of children will be made by the 
evaluating psychologist at each site based on all available data. Participants and their parents 
will each receive a $15 gift card (or comparably valued prize/compensation) for participation 
in the screening/baseline assessment. It is anticipated that some children who complete the 
screening/baseline assessment will not meet randomization criteria based on evidence of 

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intellectual disability or psychiatric functioning. In the trial of Cogmed with survivors, less than 
10% of children screened were excluded from participation for these reasons.  
 
Participants meeting criteria for randomization will be trained in the use of the Cogmed 
programs in the clinic by study personnel (see below and Appendix II). In order to avoid 
biasing the sample towards socioeconomically advantaged individuals, participants without 
dedicated access to an adequate home computer will be provided with a laptop computer or 
tablet device for the duration of the intervention, regardless of whether they are assigned to 
the adaptive or non-adaptive arms. Moreover, families without available internet access will 
be provided with wireless internet cards for the duration of the intervention. The intervention 
will consist of three to five, 15- to 45-minute sessions (younger children practice for less 
time) per week for 5 to 9 weeks (total = 25 sessions). If patients do not complete the training 
within 9 weeks, they will be removed off protocol therapy but will remain on study and will 
receive the post-intervention and follow-up assessment. Similarly, patients who do not 
complete the 25 sessions for any reason will receive the post-intervention and follow-up 
assessment unless they meet Off Study Criteria (see Section 5.0 below). Thus, using an 
intent-to-treat approach, every effort will be made to obtain post-intervention and follow-up 
data on every child who is randomized, unless they meet Off Study Criteria.  
 
To assist participants as they complete the intervention, a treatment “coach” will be available 
to parents and children by phone throughout the intervention period. Weekly phone contact 
with the coaches will be scheduled so that compliance and feasibility data may be collected 
and so that any problems (e.g., training issues, adverse events, technical problems) can be 
addressed efficiently. Of note, Cogmed routinely provides technical assistance to individuals 
using the programs at no additional cost. Additionally, to promote compliance and maintain 
children’s interest in the program, participants will earn $10 gift cards (or comparably valued 
prizes/compensation) after completion of approximately each third of the training (total = 
$30). This incentive schedule is similar to the one used in the trial of this program in survivors 
of childhood cancer, and was associated with a compliance rate of 85%.  
 
4.4 
Computerized Cognitive Training Treatment  
Cogmed RM and Cogmed JM (see Appendix II) are computer programs that are installed 
from a CD-ROM and compatible with most Windows-based computers. They are 
commercially available to qualified practitioners through Cogmed; Dr. Hardy has already 
received training and certification as a practitioner and has experience treating children on 
a previous NCI study (R03-CA132570). The program consists of twelve visually engaging 
and interesting exercises that target skills involving visuo-spatial and verbal WM. 
Difficulty of the tasks is automatically adjusted on a trial-by-trial basis throughout each 
training session to match a child’s current WM such that as the child becomes more 
proficient, the exercises become more difficult. Cogmed RM is designed for children aged 
8 to 18 and Cogmed JM is the preschool version of the computer program (ages 4 to 7). 
 
Throughout training, the child’s assigned intervention coach has online access to detailed 
information about his or her training sessions. Specifically, coaches can see when and how 
long children trained, and the outcome (pass or fail) of each of the 120 trials children 
complete during a single training session. Using this information, coaches can modify the 
training sequence or make suggestions to the child and/or parent about how progress can 
be maximized (e.g., by taking a short break after three failed trials to prevent frustration). 
Strategies to promote treatment success and compliance are based on cognitive-behavioral 
principles (e.g., positive reinforcement, self-encouragement, problem-solving). Families 
will have phone meetings at least once per week with an intervention coach to ensure 

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compliance, track progress, provide feedback and answer any questions that may have 
arisen during treatment.  
 
4.5 
Neuropsychological and Behavioral Measures  
 
4.5.1 
Study Instruments 
The instruments used are listed in Table 1 below, and described in Appendix III. 
If your institution does not have access to all test instruments specified in 
Appendix III, it may be possible to borrow the test materials. Loaning of test kits 
will be dependent upon availability. Please note that only English test kits and 
materials are available for loan. At least 3 weeks prior to the date of assessment, 
contact 
 
 
 
 
 
 
 
 
with your request for materials.  
 
4.5.2 
Baseline Testing, with and without Optional Psychologist Portion 
The full list of study assessments to be completed at baseline are presented below 
in Table 1.  
 
For sites participating in the psychologist portion (optional): a brief 
neuropsychological/behavioral assessment will be conducted at baseline to 
establish that children are cognitively and psychologically eligible for 
participation, and in order to document individual and family variables that later 
may be found to relate to feasibility. Specifically, children will complete 
neuropsychological measures and a psychiatric interview will be conducted by a 
study psychologist at each site to determine whether the child meets criteria for 
any DSM-5 mental health disorder that, in the psychologist’s opinion, would 
contraindicate participation in the intervention. For example, a child with 
significant performance anxiety may be excluded if the evaluating psychologist 
feels that study participation was likely to increase the child’s anxiety during 
training. Thus, the intent would be to avoid enrolling children for whom cognitive 
training may exacerbate existing, clinically significant mood or behavioral 
symptoms. The baseline assessment will require 60-90 minutes.  
 
Note that, if a site is not participating in the optional psychologist-administered 
battery, a member of the child’s medical or psychosocial support team may 
provide approval for the child to participate in the study, based on available 
information about the child’s current or prior mental health. Dr. Hardy may be 
contacted prior to participant enrollment with any questions about what parameters 
should be considered before approving a child for participation. 
 
4.5.3 
Post-Intervention and 6-month Follow-up Assessments 
CogState, a brief, computerized assessment of memory functioning will be 
administered following the intervention (at approximately 5 months post-CRT) 
and again 6 months following the completion of the intervention. The 
computerized testing can be administered by any individual who completes online 
training for CogState or who has already completed online training for any of the 
other COG trials for which CogState has been used (i.e., AAML1331, AALL1131, 
ACCL0922). Parents/caregivers will also asked to complete the BRIEF and the 
Feasibility Interview at these timepoints. Testing will require approximately 20-30 
minutes at each timepoint. The child will also complete the Feasibility Interview 

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at the post-intervention assessment, and the parent will complete the Computer 
Use questionnaire and ABAS-3 at the 6-month follow-up. 
 
Optional Testing: It is highly recommended that the psychologist-administered 
measures also be administered, if possible, following the intervention (at 
approximately 5 months post-CRT) and again 6 months following the completion 
of the intervention. Measures were selected to be compatible with COG 
ALTE07C1, when possible, in order to be consistent with the Behavioral Science 
Committee’s resolution to streamline assessments, promote higher compliance 
with neurocognitive study aims, reduce costs, and increase the ability to compare 
findings across COG-supported studies. The psychologist-administered post-
intervention assessments will require about 30 minutes each. At each institution, a 
psychologist or neuropsychologist will oversee this optional testing.  
 
4.6 
Feasibility Interview 
For a previous trial with survivors of childhood cancer (R03-CA132570), a 13-item survey 
(see Appendix VA and VB) for parents and children was developed and utilized to assess 
technical feasibility, adherence, satisfaction, and ease-of-use. The Feasibility Interview will 
be completed by the parent by phone following Session 12. Additionally, both child and parent 
will complete a second interview during the post-intervention assessment. See Table 1 below. 
 
4.7 
Testing Schedule 
Table 1 presents the assessments to be completed by study timepoint. See Appendix III for 
a description of the study instruments. The assessments should be administered in the order 
listed in Table 1. 
 
Table 1: Testing Schedule 
Testing Session 
Child 
Parent 
 
Baseline 
- CogState 
 
Optional (psychologist-administered) measures: 
- WISC-V (Block Design, Vocabulary, Digit Span, 
Coding, Symbol Search, and Spatial Span subtests)  
- CMS (Dot Location and Faces subtests) 
- CVLT-C 
- Instructional WM 
- Socioeconomic Status Measure 
- Computer Use Questionnaire 
- COG Language Questionnaire 
- BASC-3  
- BRIEF  
- ABAS-3  
- BIS 
Following CT Session 12 
 
- Feasibility Interview 
 
Post-Intervention 
-  Feasibility Interview 
-  CogState 
 
Optional (psychologist-administered) measures:  
- WISC-V (Digit Span, Coding, Symbol Search, and 
Spatial Span subtests) 
- CMS (Dot Location and Faces subtests) 
- Instructional WM 
 
- Feasibility Interview 
- BRIEF 
 
 
6-Month Follow-Up 
- CogState 
 
Optional (psychologist-administered) measures: 
- WISC-V (Digit Span, Coding, Symbol Search, and 
Spatial Span subtests) 
- CMS (Dot Location and Faces subtests) 
- CVLT-C 
- Instructional WM 
 
- Computer Use Questionnaire 
- BRIEF 
- ABAS-3 
 
 

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4.8 
Feedback to Participants 
The study psychologist at each site will inform the health care providers of participants 
who receive scores in the bottom 7% (i.e., 1.5 SD below the mean) relative to the 
standardization sample on the WISC-V estimated IQ, WISC-V Working Memory Index, 
WISC-V Processing Speed Index, or the BRIEF Metacognitive or Behavioral Regulation 
Indices, given that extreme scores on these measures may reflect significant difficulties 
that can interfere with learning. When children receive scores at or more extreme than 1.5 
SD from the mean, their health care team will be informed of the results in the form of a 
letter listing the scores of concern. In this way, the health care team can follow up with 
families to determine if further assessment is warranted based on whether or not families 
are observing difficulties in their child’s functioning at home or in school, and make a 
referral as they would normally do when families report concerns of this kind.  
 
This feedback requirement will not apply to sites that are not completing the optional 
psychologist-administered portion of the testing visits. 
 
 
5.0 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA  
 
5.1 
Criteria for Removal from Protocol Therapy 
a) Refusal of further protocol treatment by patient/parent/guardian. 
b) Completion of planned study treatment. 
c) Physician determines it is in patient’s best interest. 
d) Patient does not complete the computerized cognitive training within 9 weeks. 
e) Development of seizures or change in functional status that will prevent patient from 
completing further treatment or assessments. 
f) Progressive disease or relapse 
 
5.2 
Off Study Criteria 
a) Death 
b) Lost to follow-up (prior to 6-month follow-up testing) 
c) Completion of all study assessments. 
d) Withdrawal of consent for any further data submission. 
e) Patient did not meet criteria to proceed to randomization. 
f) Patient is started on psychostimulant medications or change in dose of psychostimulant 
medication. 
g) Patient refuses randomization 
 
 
6.0 
STATISTICAL CONSIDERATIONS 
 
6.1 
Statistical Design 
This primary goal of the study is to establish feasibility of a home-based computerized 
cognitive training program Cogmed, on patients 6 to 16 years of age with pediatric brain 
tumors and undergoing CRT. Within approximately 2-4 months of completing CRT, patients 
meeting criteria for randomization will be randomized 1:1 to Arm A the intervention arm 
(adaptive program) or Arm B the active control arm (non-adaptive program). Randomization 
will be stratified by known risk factors including age (< 8 years vs. ≥ 8 years), treatment 
intensity (whole brain vs. focal RT) and also by Coach (A versus B).2,48 Randomized patients 
are expected to complete 25 training sessions over 5 to 9 weeks, and then complete a post-

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intervention testing and a 6-month follow-up testing. The treating psychologist and/or the 
individual performing computerized cognitive testing must be blinded for testing. 
 
6.2 
Patient Accrual and Expected Duration of Trial 
The study accrual target is 60 randomized patients evaluable for the primary endpoint of 
intervention compliance. It is anticipated that some children who complete the baseline 
assessment will not meet the eligibility criteria for randomization based on evidence of 
intellectual disability or psychiatric functioning. In the trial of Cogmed with survivors, less 
than 10% of children screened were excluded from participation for these reasons. 
 
Randomized patients who are removed off protocol therapy for medical reasons 
(relapse/progression, death, physician’s determination in the patient’s best interest, 
development of seizures or other change in functional status, or starting or changing the 
dose of psychostimulants) would be deemed inevaluable for the primary compliance 
endpoint. Therefore, using an estimate of 15% for screen failures and inevaluable patients, 
we project that we may need to enroll up to 71 participants.  
 
With enrollment open to all institutions within COG, we anticipate that our goal of accruing 
60 evaluable patients from those eligible is feasible within two years after Amendment #1 is 
activated. There are very few on-therapy cognitive intervention trials from which to base an 
estimate of feasibility, though at St. Jude Children’s Research Hospital, recruitment to 
SJMB03, which has a reading-based intervention program embedded in the study, was 
strong. Specifically, 64% of children enrolled on the protocol have been randomized to either 
the treatment or standard-of-care arm of that protocol. The primary reasons that children were 
not randomized, in order of frequency, included 1) age outside the inclusion criteria, 2) poor 
medical status (including posterior fossa syndrome), 3) non-English speaking, and 4) parents 
did not consent to randomization (Shawna Palmer, study PI, personal communication on Oct. 
29, 2010). We anticipate that parents of children receiving cranial radiation therapy will be 
aware of the potential risks of neurocognitive late effects, and that at least one quarter of these 
parents will be willing to have their children participate in a cognitive intervention trial, 
particularly since it is home-based. The project has the strong support of the Behavioral 
Sciences Committee, and we have identified key personnel at each site who can help to 
inform colleagues about the study and motivate referrals of eligible patients.  
 
6.3 
Statistical Analysis Methods 
 
6.3.1 
Endpoints 
Primary endpoint is intervention compliance defined as at least 80% of sessions 
completed (i.e., completing at least 20 sessions within 9 weeks of starting training). 
The target is to have at least 75% of the participants compliant with intervention. 
 
Secondary endpoints on subjective and objective measures of attention and WM 
include parent-rated executive function and WM using the Metacognition 
subscales from the BRIEF, the measure of executive function using the Groton 
Maze Learning task of the CogState battery and measure of WM by the one-back 
task from CogState. In addition, for participants who have participated in the 
optional psychologist-administered battery, we will analyze the measure of WM 
using Digit Span from Wechsler Intelligence Scales, measures of verbal and visual 
memory using Dot Location from Children’s Memory Scale Spatial Span from 
Wechsler Scale. 
 

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Secondary endpoints on feasibility are the item responses to the 13-item Feasibility 
Interview assessing technical feasibility, adherence, satisfaction and ease of use. 
 
6.3.2 
Power Considerations 
Because there is no evidence that a home-based, computerized CT program will be 
feasible for this population and in multiple COG institutions, our primary aims are 
to evaluate the program’s ease of use and participant compliance, which we will 
define as 80% of sessions completed within 9 weeks of starting treatment. The goal 
is to have at least 75% of participants being compliant (i.e., completing 20 or more 
of the 25 sessions). Randomized patients who are removed off protocol therapy for 
medical reasons (relapse/progression, death, physician’s determination in the 
patient’s best interest, development of seizures or other change in functional status, 
or starting or changing the dose of psychostimulants) would be deemed inevaluable 
for the primary compliance endpoint. With 60 evaluable participants, if the true 
compliance rate in the study participants is 59%, the power to detect such decrease 
from the target 75% compliance rate is 0.82. Power consideration is based on a Z-test 
for binomial proportion with continuity correction at 1-sided level of 0.05.  
 
6.3.3 
Analysis Plan 
Compliance rate (the portion of patients who complete at least 80% of the sessions 
within 9 weeks) will be calculated for the overall study population and each arm 
separately. Z-test for binomial proportion with continuity correction will be used 
to examine if the overall compliance rate is lower than the target of 75%. 
Confidence intervals of the estimated compliance rate will be constructed for the 
overall study population and for each arm separately. We will use Fisher’s exact 
test to examine if there is any significant difference in the compliance rate between 
the 2 arms. Compliance data on the number of sessions completed for all patients 
and for patients on each arm will also be described by summary statistics such as 
mean or median, and compared between the 2 arms by two-sample t-test or 
Wilcoxon rank sum test. We will use descriptive and summary statistics to report 
parent and child ratings of the intervention’s technical feasibility, ease-of-use, and 
satisfaction across the three time-points that this information is collected. In 
addition, we will use descriptive and summary statistics to detail the total number 
of patients enrolled, determine rates and reasons for non-eligibility and patient 
refusal for randomization, characterize socioeconomic status of the parents and 
computer usage for the patients and evaluate the number and type of adverse 
incidents reported through the questionnaires (if any). We will use a series of t-
tests (for continuous variables) and Chi-square tests or Fisher’s exact tests (for 
non-continuous variables) to examine potential differences between eligible 
patients who accept or decline to be randomized to the treatment phase, between 
participants who are compliant (i.e., 80% of sessions completed) and 
noncompliant, and for other medical, psychosocial, and contextual factors.  
 
The analysis of preliminary efficacy will be conducted on an intent-to-treat basis. 
We will use descriptive/summary statistics to summarize the objective and the 
subjective measures of attention and WM in each arm and the differences between 
the 2 arms on the post-intervention/6-month assessment or on the difference 
between the post-intervention/6-month assessment and the baseline assessment. 
Linear regression models using the post-intervention/6-month assessment as 
outcome will also be used to estimate the effect size of intervention with 
adjustment for potential confounders including the baseline assessment. Linear 

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mixed model analyses which include measures at all time-points will also be 
considered to examine and estimate the effect size of the intervention with 
adjustment for within-patient dependence of the measures over time. We will also 
explore in various regression models which medical, psychosocial, and 
environmental factors are related to feasibility, acceptability, and short-term 
efficacy of the intervention. In particular, age of the participants and 
socioeconomic status measures which are potentially important predictors will be 
examined in these models. 
 
6.4 
Gender and Minority Accrual Estimates 
The gender and minority distribution of the study population is expected to be: 
 
Racial Categories 
DOMESTIC PLANNED ENROLLMENT  
Ethnic Categories 
Not Hispanic or Latino 
Hispanic or Latino 
 
Total 
Female 
Male 
Female 
Male 
American Indian/ Alaska Native 
0 
0 
0 
0 
0 
Asian 
1 
0 
0 
0 
1 
Native Hawaiian or Other Pacific Islander 
0 
0 
0 
0 
0 
Black or African American 
4 
5 
0 
0 
9 
White  
16 
27 
3 
5 
51 
More Than One Race 
0 
0 
0 
0 
0 
Total 
21 
32 
3 
5 
61 
 
Racial Categories 
INTERNATIONAL (including Canadian 
participants) PLANNED ENROLLMENT  
Ethnic Categories 
Not Hispanic or Latino 
Hispanic or Latino 
 
Total 
Female 
Male 
Female 
Male 
American Indian/ Alaska Native 
0 
0 
0 
0 
0 
Asian 
0 
1 
0 
0 
1 
Native Hawaiian or Other Pacific Islander 
0 
0 
0 
0 
0 
Black or African American 
0 
0 
0 
0 
0 
White  
3 
6 
0 
0 
9 
More Than One Race 
0 
0 
0 
0 
0 
Total 
3 
7 
0 
0 
10 
 
 
7.0 
RECORDS AND REPORTING 
 
See the Case Report Forms posted on the COG web site with each protocol under “Data Collection”. 
A submission schedule is included. 
 
7.1 
CDUS 
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0. 
Cumulative protocol- and patient-specific CDUS data will be submitted quarterly to CTEP 
by electronic means. Reports are due January 31, April 30, July 31 and October 31. CDUS 
reporting is not a responsibility of institutions participating in this trial. 
 
 
 

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REFERENCES 
1. Hardy KK, Willard VW, Bonner MJ: Computerized cognitive training in survivors of childhood cancer: A 
pilot study. Journal of Pediatric Oncology Nursing, in press 
2. Spiegler BJ, Bouffet E, Greenberg ML, et al: Change in neurocognitive functioning after treatment with 
cranial radiation in childhood. Journal of Clinical Oncology 22:706-713, 2004 
3. Maddrey AM, Bergeron JA, Lombardo ER, et al: Neuropsychological performance and quality of life of 10 
year survivors of childhood medulloblastoma. Journal of Neuro-Oncology 72:245-253, 2005 
4. Zebrack BJ, Gurney JG, Oeffinger K, et al: Psychological outcomes in long-term survivors of childhood 
brain cancer: A report from the Childhood Cancer Survivors Study. Journal of Clinical Oncology 22:999-
1006, 2004 
5. Reimers TS, Ehrenfels S, Mortensen EL, et al: Cognitive deficits in long-term survivors of childhood brain 
tumors: Identification of predictive factors. Medical and Pediatric Oncology 40:26-34, 2003 
6. Di Pinto M, Conklin HM, Li C, et al: Investigating verbal and visual auditory learning after conformal 
radiation therapy for childhood ependymoma. International Journal of Radiation Oncology, Biology, 
Physics, in press September 22, 2009 
7. Mulhern RK, Palmer SL: Neurocognitive late effects in pediatric cancer. Current Problems in Cancer 
27:177-197, 2003 
8. Mulhern RK, Merchant TE, Gajjar A, et al: Late neurocognitive sequelae in survivors of brain tumors in 
childhood. The Lancet Oncology 5:399-408, 2004 
9. Butler RW: Attentional processes and their remediation in childhood cancer. Medical and Pediatric 
Oncology Supplement 1:75-78, 1998 
10. Dennis M, Hetherington CR, Spiegler BJ: Memory and attention after childhood brain tumors. Medical and 
Pediatric Oncology Supplement 1:25-33, 1998 
11. Reddick WE, White HA, Glass JO, et al: Developmental model relating white matter volume to 
neurocognitive deficits in pediatric brain tumor survivors. Cancer 97:2512-2519, 2003 
12. Palmer SL, Reddick WE, Gajjar A: Understanding the cognitive impact on children who are treated for 
medulloblastoma. Journal of Pediatric Psychology 32:1040-1049, 2007 
13. Fry AF, Hale S: Processing speed, working memory, and fluid intelligence: Evidence for a developmental 
cascade. Psychological Science 7:237-241, 1996 
14. Schatz J, Kramer JH, Ablin A, et al: Processing speed, working memory, and IQ: A developmental model 
of cognitive deficits following cranial radiation therapy. Neuropsychology 14:189-200, 2000 
15. Gathercole SE: Cognitive approaches to the development of short-term memory. Trends in Cognitive 
Science 3:410-419, 1999 
16. Swanson HL, Beebe-Frankenberger M: The relationship between working memory and mathematical 
problem solving in children at risk and not at risk for serious math difficulties. Journal of Educational 
Psychology 96:471-491, 2004 
17. McCallum RS, Bell SM, Wood MS, et al: What is the role of working memory in reading relative to the big 
three processing variables (orthography, phonology, and rapid naming)? Journal of Psychoeducational 
Assessment 24:243-259, 2006 
18. Hutton UMZ, Towse JN: Short-term memory and working memory as indices of children's cognitive skills. 
Memory 9:383-394, 2001 
19. LeBlanc MD, Weber-Russell S: Text integration and mathematical connections: A computer model of 
arithmetic word problem solving. Cognitive Science 20:357-407, 1996 
20. Abdullah S, Qaddoumi I, Bouffet E: Advances in the management of pediatric central nervous system 
tumors. Annals of New York Academy of Sciences 1138:22-31, 2008 
21. Packer RJ: Childhood brain tumors: Accomplishments and ongoing challenges. Journal of Child Neurology 
23:1122-1127, 2008 
22. Armstrong FD, Briery BG: Childhood cancer and the school, in Brown RT (ed): Handbook of Pediatric 
Psychology in School Settings. New York, Lawrence Earlbaum, 2004, pp 263-281 
23. Meyers CA, Weitzner MA, Valentine AD, et al: Methylphenidate therapy improves cognition, mood, and 
function of brain tumor patients. Journal of Clinical Oncology 16:2522-2527, 1998 

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Page 26 
24. Mulhern RK, Khan RB, Kaplan S, et al: Short-term efficacy of Methylphenidate: A randomized, double-
blind, placebo-controlled trial among survivors of childhood cancer. Journal of Clinical Oncology 22:4795-
4803, 2004 
25. Thompson SJ, Leigh L, Christensen R, et al: Immediate neurocognitive effects of Methylphenidate on 
learning-impaired survivors of childhood cancer. Journal of Clinical Oncology 19:1802-1808, 2001 
26. Conklin HM, Helton S, Ashford J, et al: Predicting methylphenidate response in long-term survivors of 
childhood cancer: A randomized, double-blind, placebo-controlled, crossover trial. Journal of Pediatric 
Psychology, in press 
27. Butler RW, Copeland DR: Attentional processes and their remediation in children treated for cancer: A 
literature review and the development of a therapeutic approach. Journal of the International 
Neuropsychological Society: JINS 8:115-124, 2002 
28. Butler RW, Copeland DR, Fairclough DL, et al: A multicenter, randomized clinical trial of a cognitive 
remediation program for childhood survivors of a pediatric malignancy. Journal of Consulting and Clinical 
Psychology 76:367-378, 2008 
29. Patel SK, Katz ER, Richardson R, et al: Cognitive and problem solving training in children with cancer: A 
pilot project. Journal of Pediatric Hematology/Oncology 31:670-677, 2009 
30. Butler RW, Haser JK: Neurocognitive effects of treatment for childhood cancer. Mental Retardation and 
Developmental Disabilities Research Reviews 12:184-191, 2006 
31. Wilson JRF, Green A: Acute traumatic brain injury: A review of recent advances in imaging and 
management. European Journal of Trauma and Emergency Surgery 35:176-185, 2009 
32. Eack SM, Hogarty GE, Greenwald DP, et al: Cognitive enhancement therapy improves emotional 
intelligence in early course schizophrenia: Preliminary effects. Schizophrenia Research 89:308-311, 2007 
33. Moore IM, Hockenberry M, Kaemingk K, et al: Math intervention for children with acutelymphoblastic 
leukemia. Oncology Nursing Forum 32:168, 2005 
34. Kerns KA, Eso K, Thomson J: Investigation of a direct intervention for improving attention in young 
children with ADHD. Developmental Neuropsychology 16:273-295, 1999 
35. Klingberg T, Fernell E, Olesen PJ, et al: Computerized training of working memory in children with ADHD 
- A randomized, controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry 
44:177-186, 2005 
36. Klingberg T, Forssberg H, Westerberg H: Training of working memory in children with ADHD. Journal of 
Clinical and Experimental Neuropsychology 24:781-791, 2002 
37. Slate SE, Meyer TL, Burns WJ, et al: Computerized cognitive training for severely emotionally disturbed 
children with ADHD. Behavior Modification 22:415-437, 1998 
38. Holmes J, Gathercole SE, Dunning DL: Adaptive training leads to sustained enhancement of poor working 
memory in children. Developmental Science 12:F9-F15, 2009 
39. Holmes J, Gathercole SE, Place M, et al: Working memory deficits can be overcome: Impacts of training 
and medication on working memory in children with ADHD. Applied Cognitive Psychology, in press 
40. McNab F, Varrone A, Farde L, et al: Changes in cortical dopamine D1 receptor binding associated with 
cognitive training. Science 323:800-802, 2009 
41. Thorell LB, Lindqvist S, Bergman S, et al: Training and transfer effects of executive functions in preschool 
children. Developmental Science 11:969-976, 2008 
42. Westerberg H, Jacobaeus H, Hirvikoski T, et al: Computerized working memory training after stroke: A 
pilot study. Brain Injury 21:21-29, 2007 
43. Mezzacappa E, Buckner JC: Working memory training for children with attention problems or hyperactivity: 
A school-based pilot study. School Mental Health, in press 
44. Cogmed: Qualified Practitioner Training Manual. Naperville, IL, Cogmed America Inc, 2007  
45. Adams W, Sheslow D: Wide Range Assessment of Memory and Learning Administration and Technical 
Manual (ed 2nd). Wilmington, DE, Wide Range Inc, 2003  
46. Conners CK: Conners 3rd Edition Manual. Toronto, ON, Multi-Health Systems Inc., 2008  
47. Hardy KK, Willard VW, Bonner MJ: Computerized working memory training with survivors of childhood 
cancer. Presented at the Annual Meeting of the Society of Developmental and Behavioral Pediatrics, 
Portland, OR, 2009, October 

THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY                         ACCL10P1 
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48. Ris MD, Packer R, Goldwein J, et al: Intellectual outcome after reduced-dose radiation therapy plus adjuvant 
chemotherapy for medulloblastoma: A Children's Cancer Group study. Journal of Clinical Oncology 
19:3470-3476, 2001 
49. Wechsler D: Wechsler Adult Intelligence Scale - 3rd edition. San Antonio, TX, The Psychological 
Corporation, 1997  
50. Wechsler D: WPPSI-III: Administration and scoring manual. San Antonio, TX, The Psychological 
Corporation, 2002  
51. Wechsler D: Wechsler Intelligence Scale for Children - 4th Edition. San Antonio, TX, The Psychological 
Corporation, 2003  
52. Cohen MJ: Children's Memory Scale. San Antonio, TX, The Psychological Corporation, 1995  
53. Delis D, Kaplan E, Kramer J, et al: California Verbal Learning Test–II. San Antonio, TX, The Psychological 
Corporation, 2000  
54. Delis DC, Kramer KH, Kaplan E, et al: Manual for the California Verbal Learning Test – Children’s Version. 
San Antonio, TX, Psychological Corporation, 1994  
55. Falleti MG, Maruff P, Collie A, et al: Practice effects associated with the repeated assessment of cognitive 
function using the CogState battery at 10-minute, one week and one month test-retest intervals. Journal of 
Clinical and Experimental Neuropsychology 28:1095-1112, 2006 
56. Maruff P, Thomas E, Cysique L, et al: Validity of the CogState brief battery: Relationship to standardized 
tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS 
dementia complex. Archives of Clinical Neuropsychology 24:165-178, 2009 
57. Snyder AM, Maruff P, Pietrzak RH, et al: Effect of treatment with stimulant medication on nonverbal 
executive function and visuomotor speed in children with attention deficit/hyperactivity disorder (ADHD). 
Child Neuropsychology 14:211-226, 2008 
58. Betts J, McKay J, Maruff P, et al: The development of sustained attention in children: The effect of age and 
task load. Child Neuropsychology 12:205-221, 2006 
59. Collie A, Makdissi M, Maruff P, et al: Cognition in the days following concussion: Comparison of 
symptomatic versus asymptomatic athletes. Journal of Neurology, Neurosurgery, and Psychiatry 77:241-
245, 2006 
60. Cysique LA, Maruff P, Darby D, et al: The assessment of cognitive function in advanced HIV-1 infection 
and AIDS dementia complex using a new computerised cognitive test battery. Archives of Clinical 
Neuropsychology 21:185-194, 2006 
61. Bangirana P, Giordani B, John CC, et al: Immediate neuropsychological and behavioral benefits of 
computerized cognitive rehabilitation in Ugandan pediatric cerebral malaria survivors. Journal of 
Developmental and Behavioral Pediatrics 30:310-318, 2009 
62. Vardy J, Wong K, Yi QL, et al: Assessing cognitive function in cancer patients. Supportive Care in Cancer 
14:1111-1118, 2006 
63. Reynods CR, Kamphaus RW: Behavior Assessment Scale for Children, Second Edition. Circle Pines, MN, 
AGS, 2004  
64. Gioia GA, Isquith PK, Guy SC, et al: Behavior Rating Inventory of Executive Function (BRIEF). Lutz, FL, 
PAR, INC, 2000  
65. Isquith PK, Gioia GA, Espy KA: Executive function in preschool children: Examination through everyday 
behavior. Developmental Neuropsychology 26:403-422, 2004 
66. Harrison P, Oakland T: Adaptive Behavior Assessment System, Second Edition. San Antonio, TX, The 
Psychological Corporation, 2003  
67. Bird HR, Canino GJ, Davies M, et al: The Brief Impairment Scale (BIS): A multidimensional scale of 
functional impairment for children and adolescents. Journal of the American Academy of Child and 
Adolescent Psychiatry 44:699-707, 2005 
 
 

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APPENDIX I: CTEP AND CTSU REGISTRATION PROCEDURES 
 
CTEP INVESTIGATOR REGISTRATION PROCEDURES 
 
Food and Drug Administration (FDA) regulations and National Cancer Institute (NCI) policy 
require all individuals contributing to NCI-sponsored trials to register and to renew their registration 
annually. To register, all individuals must obtain a Cancer Therapy Evaluation Program (CTEP) 
Identity and Access Management (IAM) account (https://ctepcore.nci.nih.gov/iam). In addition, 
persons with a registration type of Investigator (IVR), Non-Physician Investigator (NPIVR), or 
Associate Plus (AP) (i.e., clinical site staff requiring write access to OPEN, RAVE, or TRIAD or 
acting as a primary site contact) must complete their annual registration using CTEP’s web-based 
Registration and Credential Repository (RCR) (https://ctepcore.nci.nih.gov/rcr). Documentation 
requirements per registration type are outlined in the table below. 
 
Documentation Required 
IVR 
NPIVR 
AP 
A 
FDA Form 1572 
 
 
Financial Disclosure Form 
 
 
 
NCI Biosketch (education, training, 
employment, license, and certification) 
 
 
 
HSP/GCP training 
 
 
 
Agent Shipment Form (if applicable) 
 
CV (optional) 
 
 
 
 
An active CTEP-IAM user account and appropriate RCR registration is required to access all 
CTEP and CTSU (Cancer Trials Support Unit) websites and applications. In addition, IVRs and 
NPIVRs must list all clinical practice sites and IRBs covering their practice sites on the FDA 
Form 1572 in RCR to allow the following: 
• 
Added to a site roster 
• 
Assigned the treating, credit, consenting, or drug shipment (IVR only) tasks in OPEN 
• 
Act as the site-protocol PI on the IRB approval 
• 
Assigned the Clinical Investigator (CI) role on the Delegation of Tasks Log (DTL). 
 
Additional information can be found on the CTEP website at: 
https://ctep.cancer.gov/investigatorResources/default.htm.  For questions, please contact the RCR 
Help Desk by email at RCRHelpDesk@nih.gov. 
 
 

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CTSU REGISTRATION PROCEDURES 
 
This study is supported by the NCI Cancer Trials Support Unit (CTSU).  
 
Requirements for ACCL10P1 Site Registration: 
 
• IRB approval (For sites not participating via the NCI CIRB; local IRB documentation, an IRB-signed 
CTSU IRB Certification Form, Protocol of Human Subjects Assurance Identification/IRB 
Certification/Declaration of Exemption Form, or combination is accepted ) 
• IROC Credentialing Status Inquiry (CSI) Form 
NOTE: For studies with a radiation and/or imaging (RTI) component, the enrolling site must be 
aligned to a RTI provider. To manage provider associations access the Provider Association tab on 
the CTSU website at https://www.ctsu.org/RSS/RTFProviderAssociation, to add or remove 
associated providers. Sites must be linked to at least one IROC credentialed provider to participate 
on trials with an RT component.  
 
Submitting Regulatory Documents: 
 
Submit required forms and documents to the CTSU Regulatory Office, where they will be entered and 
tracked in the CTSU RSS.  
 
Regulatory Submission Portal: www.ctsu.org (members’ area) → Regulatory Tab 
→ Regulatory Submission  
 
When applicable, original documents should be mailed to: 
CTSU Regulatory Office 
1818 Market Street, Suite 3000 
Philadelphia, PA 19103 
 
Institutions with patients waiting that are unable to use the Portal should alert the CTSU Regulatory Office 
immediately at 1-866-651-2878 in order to receive further instruction and support. 
 
Checking Your Site’s Registration Status: 
 
You can verify your site registration status on 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 
 
Note: The status given only reflects compliance with IRB documentation and institutional compliance with 
protocol-specific requirements as outlined by the Lead Network. It does not reflect compliance with 
protocol requirements for individuals participating on the protocol or the enrolling investigator’s status with 
the NCI or their affiliated networks. 

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APPENDIX II: COGMED RM AND COGMED JM  
 
Cogmed RM and Cogmed JM are computer programs installable from a CD-ROM and compatible with 
any Windows-based computer or tablet device. They are commercially available to qualified practitioners 
through Cogmed; Dr. Hardy has already received training and certification as a practitioner and has 
experience treating children on the NCI R03-CA132570 study. The program consists of twelve visually 
engaging and interesting exercises that target skills involving visuo-spatial and verbal WM. Difficulty of 
the tasks is automatically adjusted on a trial-by-trail basis throughout each training session to match a 
child’s current memory span, such that as the child becomes more proficient, the exercises become more 
difficult. Cogmed RM is designed for children aged 8 to 16. Exercises have space and robot themes with 
names such as “Decoder,” “Space Whack,” and “Visual Data Link.” For example, “Asteroids,” a visuo-
spatial WM exercise, consists of a number of asteroids floating through space. The asteroids light up in a 
random order, after which the child is asked to click on the 
asteroids in the order in which they just were highlighted. 
When done correctly, the highlighted asteroids explode. In 
“Stabilizer,” a verbal memory exercise, children hear a series 
of letters while lights illuminate with each letter. Then, when 
the letter appears on the screen, the child must select the 
correct light that was originally paired with that letter. 
Cogmed RM also contains a game, “Robo Racing,” that 
children can play at the end of each session as a reward for 
completing their session. Children are encouraged to perform 
well during their training session to earn more “energy” that 
can later be used during the reward game. Cogmed JM is the preschool version of the computer program, 
designed for children aged 4 to 7 years (see Figure 1 for an example exercise).  
 
In each version of the intervention, children complete 25 training sessions. Children are asked to complete 
between 3 and 5 sessions per week, so the total treatment time to complete 25 sessions may range from 5 to 9 
weeks. For children completing Cogmed RM, sessions typically last between 25 and 45 minutes, depending on 
the child’s working memory span. For younger children completing Cogmed JM, sessions are designed to be 
shorter in accordance with young children’s cognitive stamina; thus, younger children’s training sessions 
typically last about 15 minutes.  
 
Throughout training, the child’s intervention coach has online access to detailed information about his or 
her training sessions. Specifically, coaches can see when and how long children trained, and the outcome 
(pass or fail) of each of the trials children complete during a single training session. Using this information, 
coaches can modify the training sequence or make suggestions to the child and/or parent about how progress 
can be maximized (e.g., by taking a short break after three failed trials to prevent frustration). Families will 
have phone meetings at least once per week with an intervention coach to ensure compliance, track progress, 
provide feedback and answer any questions that may have arisen during treatment. Coaches will also have 
an assessment script for these calls, for re-evaluating medical, psychological, and environmental factors 
that may potentially be related to feasibility and efficacy of the intervention.  
 
Treatment compliance: The Cogmed programs automatically track the number and length of children’s 
sessions, along with their progress through program levels. This is accomplished through the Internet, every 
time the child logs into the program. For those families without home-internet access, they will be asked to 
connect the program after every 3rd session from a library or commercial establishment with free wireless 
internet access. To date, participants on our survivor trial (R03-CA132570) have had no difficulty uploading 
data over the course of the intervention, and thus we anticipate no difficulty in the proposed project. To promote 
compliance and maintain children’s interest in the program, participants will earn a $15 gift card (or comparably 
valued prize/compensation) for participating in the baseline testing. In addition, participants will earn $10 gift 
cards (or comparably valued prizes/compensation) after session numbers 9, 18, and 25. The participant and 
their parent will each receive $15 (gift cards/prizes) for completing the post-intervention and follow-up testing.  
 
Figure 1 Cogmed JM activity – “Ferris Wheel” 
Adapted from www.cogmed.com 

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APPENDIX III: STUDY ASSESSMENT INSTRUMENTS  
 
Note: Study measures were chosen to overlap with those used in ALTE07C1, with the addition of the 
computerized CogState battery, which was chosen given its ability to be administered repeatedly over short 
intervals with negligible practice effects. The measure assigned initially by age will be used during the 
study even if the patient could move up to the next age level. 
 
IQ* 
Attention/ 
Working Memory 
Verbal 
Memory 
General 
Parent Report 
 
 
 
 
 
WISC-V** 
(Block Design 
Vocabulary) 
CogState 
CVLT-C** Feasibility 
Interview 
Feasibility Interview  
 
CMS**  
(Dot Location and Faces) 
 
 
BASC-3* 
 
WISC-V** 
(Digit Span, Coding, Symbol 
Search, and Spatial Span subtests) 
 
 
BRIEF 
 
Instructional WM** 
 
 
ABAS-3 
 
 
 
 
BIS 
 
 
 
 
Socioeconomic Status 
Measure* 
 
 
 
 
Computer Use 
Questionnaire 
 
 
 
 
COG Language Preference 
Questionnaire 
* Baseline only 
** Optional psychologist-administered measure 
 
Patient-Completed Measures 
 
Wechsler Intelligence Scale for Children – Fifth Edition (WISC-V)49-51. The WISC-V measures 
intellectual functioning in children aged 6-16 (WISC-). For this project, the Vocabulary and Block Design 
subtests will be used at baseline only to estimate IQ. Additionally, working memory (Digit Span, Spatial 
Span), Coding and Symbol Search subtests will be administered at all time points for sites that have a 
psychologist to administer these measures. 
 
Children’s Memory Scale (CMS)52. The CMS is a test to assess verbal and visual memory in individuals 
5-16 years of age. Dot Location and faces will be administered at all timepoints for sites that have a 
psychologist to administer these measures. 
 
California Verbal Learning Test – Children’s Version (CVLT-C)53,54. The CVLT-C involves verbally 
presenting a list learning task over the course of 5 trials. The test measures multiple aspects of how verbal 
learning occurs, or fails to occur, as well as the amount of verbal material learned. The CVLT-C is designed 
for individuals 5-16 years of age. The CVLT-C will be administered at baseline and 6-month follow-up for 
sites that have a psychologist to administer these measures. 
 

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Page 32 
CogState is a computerized testing software package that offers a range of semi-automated assessment 
modules for individuals aged 6-90 (www.cogstate.com). The software can be installed on most computer 
systems and can be proctored by a research assistant with minimal training. Data are automatically 
uploaded, scored, and stored. Test batteries can be fully customized, and include tasks tapping visual motor, 
processing speed, visual attention, visual and verbal learning and memory, and working memory. A battery 
suitable for evaluating the core neurocognitive processes affected by cancer treatment would take between 
12-18 minutes. Reliability is .77 with no practice effects when testing intervals are greater than one month55. 
Age-based standard scores (mean = 100, SD 10) are computed for each task based on a normative sample 
of several hundred individuals. CogState tasks have been used successfully in trials of populations relevant 
to pediatric cancer patients56. Specifically, it has been used with attention deficit hyperactivity disorder 
participants, for which CogState tasks discriminate between those with and without the diagnosis, and those 
on and off medication57, as well as typically-developing children58. In addition, CogState has been used in 
samples of patients with concussions59, HIV/AIDS60, pediatric cerebral malaria61, and adult cancer 
patients62. CogState is also currently being used in a multi-site trial funded by NCI to examine 
neurocognitive symptoms in long-term survivors of pediatric cancer. CogState will be administered at all 
time points.  
 
Instructional Working Memory Task (Instructional WM). The Instructional WM is a brief task 
administered to children to evaluate functional application of WM skills. Children are asked to use task 
props (e.g., pencils, folders, etc.) to follow an increasingly complex set of instructions. For example, a child 
might be asked to “Pick up the blue ruler and put it in the red folder”. Scores are calculated based on a 
combination of accuracy in following the instructions weighted by how many actions the child is asked to 
perform with a single command. The instructional WM will be administered at all time points for sites that 
have a psychologist to administer these measures. 
 
Feasibility Interview: In our previous trial with survivors of childhood cancer (R03-CA132570), we 
developed a 13-item survey for parents and children assessing technical feasibility, adherence, satisfaction, 
and ease-of-use. The Feasibility Interview will be completed by the parent by phone after session 12. 
Additionally both child and parent will complete a second feasibility interview during the post-intervention 
assessment. 
 
Parent-Completed Measures 
 
COG Language Preferences Questionnaire. The child’s language preference will be determined before 
testing begins using the parent-completed COG Language Preference Questionnaire. In order for the child 
to be enrolled, it must be determined that the neuropsychological testing procedures can be completed in 
English. If a parent is unable to complete the parent-report measures in English, the child will still be 
allowed to enroll but parent-report data will not be obtained. The COG Language Preference Questionnaire 
can be accessed on the COG website at: 
https://www.cogmembers.org/Prot/ALTE07C1/ALTE07C1COGlanguageprefquestionnaire.pdf. 
 
Behavior Assessment System for Children, 3rd edition (BASC-3)63. The BASC-3 describes the behaviors, 
thoughts, and emotions of children and adolescents. The parent rating scale will be utilized for individuals 
older than 2 years and less than 18 years of age. The questionnaire yields composite and scale scores in the 
domains of externalizing, internalizing, school, and other problems as well as adaptive skills and behavioral 
symptoms. The BASC-3 will be administered only at baseline. 
 
Behavior Rating Inventory of Executive Functioning (BRIEF)64,65 is a parent-completed measure of 
behavioral executive functioning. For this study, items from the Metacognition subscales will be used. The 
BRIEF will be administered at all time points as an additional outcome measure. 
 

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Page 33 
Adaptive Behavior Assessment System, 3rd edition (ABAS-3)66. The ABAS-3 will be used for the 
assessment of adaptive skills in individuals older than 2 years and less than 18 years of age. Separate scale 
scores are available for 10 areas of adaptive skills. The ABAS-3 will be administered at baseline and 6 
months following the completion of training. 
 
Brief Impairment Scale (BIS)67. The BIS is a parent-completed, 23-item questionnaire evaluating social 
and functional impairment yielding scale scores for Interpersonal, School, and Self (personal) functioning. 
The BIS will be administered at baseline only.  
 
Feasibility Interview: In our previous trial with survivors of childhood cancer (R03-CA132570), we 
developed a 13-item survey for parents and children assessing technical feasibility, adherence, satisfaction, 
and ease-of-use. The Feasibility Interview will be completed by the parent by phone. Additionally the child 
will complete a feasibility interview during the post-intervention assessment. 
 
Socioeconomic Status Measure: The Socioeconomic Status measure is a brief measure consisting of 
questions related to parents’ marital status, education, and work. This measure will be completed by parents 
at baseline only. 
 
Computer Use Questionnaire: The Computer Use questionnaire assesses the frequency and nature of the 
child’s computer use at home and at school. It will be completed by parents at baseline and at 6-month 
follow-up. 
 
 
 
 

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APPENDIX IV: SOCIOECONOMIC STATUS MEASURE 
 
Obtain at Baseline. 
 
Subject: ___________________________           Subject ID: ___________________ 
 
Date: _____________________ 
 
We would like to ask you a few questions about yourself and your family. The questions ask about educational 
background and current work. Please answer all of the questions as completely as possible. 
 
 
1. 
Are you (please check all that apply): 
 Single: (Please specify further) 
 
Never married 
 
Separated 
 
Divorced 
 
Widowed 
 Married: (Please specify further) 
 
To the other parent of my child with brain tumor 
 
To someone else  
 Living with a significant other/partner: (Please specify further) 
 
With the other parent of my child with brain tumor 
 
With someone else  
 Not living with, but have a partner: (Please specify further) 
 
The other parent of my child with brain tumor 
 
Someone else  
 In a civil union 
 
2. 
If you are not living with the other parent of your child, how often does that parent see your child? 
 
Not applicable, I live with the other parent 
 
Less than once per month 
 
A few times per month 
 
About once per week 
 
A few times per week 
 
Almost every day 
 
3. 
What was the highest grade or level of school that the main caregiver has completed? 
 
Grade school (grades 1-8) 
 
High school, but didn’t graduate 
 
High school, completed 
 
Training after high school, other than college 
 
Some college 
 
College graduate 
 
Post graduate level 
 
Unknown 

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Page 35 
 
 
5a. 
What kind of work are you doing? (What is your occupation?) 
 
  
 
(For example: homemaker, retail sales, machinist, etc.) 
 
5b. 
What are your most important activities or duties? 
 
  
 
(For example: selling merchandise, filing, supervising, etc.) 
 
5c. 
What kind of business or industry is this? 
 
  
 
(For example: retail shoe store, automobile manufacturing, state labor department, etc.) 
 
PLEASE SKIP #6 and 7a, b, c if you are living alone. 
 
6. 
What was the highest grade or level of school your spouse/significant other has completed? 
 
Grade school (grades 1-8) 
 
High school, but didn’t graduate 
 
High school, completed 
 
Training after high school, other than college 
 
Some college 
 
College graduate 
 
Post graduate level 
 
Unknown 
 
 
 
7a.   What kind of work is your spouse (significant other) doing? (What is his/her occupation?) 
 
 
  
 
(For example: homemaker, retail sales, machinist, etc.) 
 
7b. 
What are his/her most important activities or duties? 
 
  
 
(For example: selling merchandise, filing, supervising, etc.) 
 
7c. 
What kind of business or industry is this? 
 
  
 
(For example: retail shoe store, automobile manufacturing, etc.) 
 
 
 

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APPENDIX VA: PARENT FEASIBILITY AND ACCEPTABILITY INTERVIEW 
 
Obtain Following CT Session 12 and After Training Completion  
 
Subject: ___________________________ 
 Subject ID: ___________________ 
 
Date: _______________________ 
 
  Session:  
12 
25 
 
Respondent: _______________________ 
 
 
Technical feasibility: 
 
1. Did the computer program work every time you tried it? 
 
Yes  
No 
 
 
a. If no, please describe problems: ____________________________________________ 
 
 
______________________________________________________________________ 
 
 
______________________________________________________________________ 
 
2. Did you have any problems with the computer itself?   
Yes  
No 
 
 
a. If yes, please describe problems: ___________________________________________ 
 
 
______________________________________________________________________ 
 
 
______________________________________________________________________ 
 
Adherence: 
 
 
1. How often did your child resist/protest/complain about completing exercises on the computer this month? 
 
Never  
Rarely  
Sometimes 
 
Often   
Always 
 
 
2. How did you typically respond to your child when s/he resisted doing exercises? 
 
 
______________________________________________________________________________ 
 
______________________________________________________________________________ 
 
 
 

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Version Date: 08/06/2018 
 
 
 
 
 
 
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3. Do you think your child would have completed the exercises even without the opportunity to earn a gift 
card? Why or why not? 
 
 
______________________________________________________________________________ 
 
______________________________________________________________________________ 
 
a. Which of the following might make your child more likely to complete all the exercises? 
 
_____ More money on the gift cards. 
_____ More frequent rewards. 
_____ Fewer required sessions. 
_____ Shorter sessions. 
 
Satisfaction / Ease of use: 
 
1. Using the following scale, how easy or difficult was it for your child to use the computer to do the 
exercises in the following areas? 
 
very easy 
somewhat easy    neither easy/hard 
somewhat hard  very hard 
 
a. turning on/logging in:    ________________ 
 
b. starting the program:      ________________ 
 
c. using the mouse: 
__________________ 
 
 
2. Using the following scale, how easy or difficult was it for your child to do the exercises? 
 
very easy 
somewhat easy    neither easy/hard 
somewhat hard  very hard 
 
3. Using the following scale, how often were you present with your child while s/he was doing the 
exercises? 
 
Never  
Rarely  
Sometimes 
 
Often   
Always 
 
4. Using the following scale, how often did your child experience physical pain or discomfort while 
using the computer program? 
 
Never  
Rarely  
Sometimes 
 
Often   
Always 
 
If any response other than “never”: Please describe the physical pain or discomfort your child 
experienced: ________________________________________________________ 
 
________________________________________________________________________ 
 
________________________________________________________________________ 
 
5. Using the following scale, how often did your child experience frustration while using the 
computer program? 
 
Never  
Rarely  
Sometimes 
 
Often   
Always 

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Version Date: 08/06/2018 
 
 
 
 
 
 
Page 38 
 
6. Using the following scale, how often did your child feel bored during the computer exercises? 
 
Never  
Rarely  
Sometimes 
 
Often   
Always 
 
7. Using the following scale, how often did your child enjoy completing the exercises? 
 
Never  
Rarely  
Sometimes 
 
Often   
Always 
 
8. Using the following scale, how satisfied were you with your child’s participation in the study this 
month? 
 
Very dissatisfied 
Somewhat dissatisfied    Neither     Somewhat satisfied    Very Satisfied 
 
Other comments or concerns: _____________________________________________________ 
 
_____________________________________________________________________________ 
 
_____________________________________________________________________________ 
 
 
 
For post-intervention administration only (please transcribe responses electronically): 
 
1. What suggestions do you have about how we could make participating in this intervention easier for 
children and families? 
 
 
2. What were the biggest difficulties you experienced in helping your child complete the training? 
 
 
3. In what ways were the study team (your coach, the psychologist, the research assistant) most helpful to 
you during the study and intervention? 
 
 
4. Was there anything you found unhelpful as you and your child participated? 
 
 
 

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Version Date: 08/06/2018 
 
 
 
 
 
 
Page 39 
APPENDIX VB: CHILD FEASIBILITY AND ACCEPTABILITY INTERVIEW 
 
Obtain After Training Completion  
 
Subject: ___________________________ 
 Subject ID: ___________________ 
 
Date: _______________________ 
 
  
 
 
 
1. Using the following scale, how often did you feel frustrated while using the computer program? 
 Never 
 Rarely 
 Sometimes 
 Often 
 Always 
 
2. Using the following scale, how often did you feel bored during the computer exercises? 
 Never 
 Rarely 
 Sometimes 
 Often 
 Always 
 
3. Using the following scale, how often did you enjoy the computer exercises? 
 Never 
 Rarely 
 Sometimes 
 Often 
 Always 
 
Comments: 
_____________________________________________________________________________________
___________________________________________________________________________________ 

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Version Date: 08/06/2018 
 
 
 
 
 
 
Page 40 
APPENDIX VI: COMPUTER USE QUESTIONNAIRE 
 
Obtain at Baseline and 6 months following the completion of training. 
 
1. How often does your child use a computer at school? 
a. Every day or nearly every day 
b. 2-3 times per week 
c. Once per week 
d. Occasionally, but less than once per week 
e. Very rarely 
f. Don’t know 
 
2. How often does your child use a computer at home? 
a. Every day or nearly every day 
b. 2-3 times per week 
c. Once per week 
d. Occasionally, but less than once per week 
e. Very rarely 
f. No home computer 
 
3. If your child uses a computer at home, which of the following activities does your child use the 
computer for (circle all that apply)? 
a. Homework 
b. Video games 
c. Educational activities other than homework 
d. Email or social networking 
e. Watching video content 
f. Browsing for news, entertainment, or informational content 
 
4. How many hours does your child spend on the computer each week at home? 
a. Less than 1 
b. 1-3 
c. 4-7 
d. 8-14 
e.  More than 14 hours per week 
 
 

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Version Date: 08/06/2018 
 
 
 
 
 
 
Page 41 
 
APPENDIX VII: YOUTH INFORMATION SHEETS 
 
 
INFORMATION SHEET REGARDING RESEARCH STUDY ACCL10P1 
(for children from 7 through 12 years of age) 
 
Study of Computerized Cognitive Training for Children with Brain Tumors 
 
 
1. We have been talking with you about your planned cancer treatment that includes radiation therapy 
to your head. Radiation therapy to your head is a cancer treatment that can affect your thinking, 
learning and remembering. These kinds of effects can make it harder for you to learn in school. 
 
2. We are asking you to take part in a research study because you are scheduled to get radiation therapy 
to your head to treat your cancer. A research study is when doctors work together to try out new 
ways to help people who are sick. This study will look to see if a treatment called cognitive training 
will get rid of effects on your thinking, learning and remembering you might have from the 
radiation therapy. 
 
3. Children who are part of this study will complete 25 cognitive training sessions for your thinking 
and remembering. The training sessions are different kinds of computer games. You will complete 
the sessions at home using a computer or tablet. The sessions will happen over 5 to 9 weeks. You 
will assigned to either the adaptive or non-adaptive cognitive training program. You will not be 
told which of these 2 programs you are assigned. 
 
4. Before you start the training sessions you will have some tests for your thinking, learning and 
remembering. Soon after you finish the training sessions you may have some more tests of your 
thinking, learning and remembering. And about 6 months after you have finished the training 
sessions, you may have some more tests of your thinking, learning and remembering. Then you 
will have finished being in this study. 
 
5. 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 less effects on your 
thinking and remembering from the cranial radiation therapy, but we don’t know for sure if there 
is any benefit of being part of this study. 
 
6. 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 being in this study is that you may find the training sessions 
or the testing to be boring or tiring. The study may also remind you about other problems you are 
having. 
 
7. 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. Make sure to ask your doctors any questions that you have. 
 
 
 
 

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Version Date: 08/06/2018 
 
 
 
 
 
 
Page 42 
INFORMATION SHEET REGARDING RESEARCH STUDY ACCL10P1 
(for teens from 13 through 17 years of age) 
 
Computerized Cognitive Training for Pediatric Brain Tumor Patients: A Pilot Study 
 
 
1. We have been talking with you about your planned cancer treatment that includes cranial radiation 
therapy. Cranial radiation therapy is a cancer treatment that can affect your ability to think, learn 
and remember. These kinds of effects can make it harder for you to learn in school. 
 
2. We are asking you to take part in a research study because you are scheduled to get cranial radiation 
therapy to treat your cancer. A research study is when doctors work together to try out new ways 
to help people who are sick. This study will look to see if a treatment called cognitive training will 
get rid of effects on your thinking, learning and remembering you might have from the cranial 
radiation therapy.  
 
3. Children and teens who are part of this study will complete 25 cognitive training sessions. The 
training sessions are different kinds of computer games. You will complete the sessions at home 
using a computer or tablet. The sessions will happen over 5 to 9 weeks. You will assigned to either 
the adaptive or non-adaptive cognitive training program. You will not be told which of these 2 
programs you are assigned. 
 
4. Before you start the training sessions you will have some tests for your thinking, learning and 
remembering. Soon after you finish the training sessions you may have some more tests of your 
thinking, learning and remembering. About 6 months after you have finished the training sessions, 
you may have some more tests of your thinking, learning and remembering. Then you will have 
finished being in this study. 
 
5. 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 less effects on your 
thinking, learning and remembering from the cranial radiation therapy, but we don’t know for sure 
if there is any benefit of being part of this study. 
 
6. 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 being in this study is that you may find the training sessions 
or the testing to be boring or tiring. The study may also remind you about other problems you are 
having. 
 
7. 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. Make sure to ask your doctors any questions that you have.