Goal Management Training for Adult Survivors of Childhood Leukemia and Non-Hodgkins Lymphoma With Neurocognitive Sequelae

Study Overview
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Brief Summary
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Survivors of childhood cancer are at risk for developing neurocognitive sequelae. Multiple meta-analyses demonstrate significant deficits in overall intellectual abilities, academic functioning and specific cognitive skills among survivors of childhood cancer treated with intrathecal chemotherapy only and/or cranial irradiation. Preventing neurocognitive deficits is therefore of great importance. Unfortunately, intervention studies for this group of survivors are scarce. The main aim of this randomized controlled trial is to determine the efficacy of Goal Management Training (GMT) as a group-based treatment program for 60 adult survivors of childhood leukemia, and non Hodgkins lymphoma, diagnosed between 1980 and 2017 at an age below 18, with attention and executive function deficits. The participants will be randomized to one treatment group (GMT), and one waitlist condition followed by one active control intervention, the Brain health workshop (BHW), which has a psycho-educative approach. The follow-up time from diagnosis will be ≥5 years and the age at survey 18-40 years. The study will expand the knowledge base on treatment factors important in improving cognitive function. Results from this study can be implemented in rehabilitation for the young adult survivors of childhood leukemia, and non Hodgkins lymphoma, which will be of importance for their future educational and work-related functioning.

Detailed Description
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Effect of the GMT/waitlist conditions will be assessed through self-reported and objective measures of neuropsychological function, quality of life and health measurements. To avoid extra training effects of neuropsychological testing on participants allocated to waitlist/BHW, assessment following BHW (approximately one-year post T1) will consist of self-report measures only. Patients in all groups will be reassessed within 14 days post intervention (T2), and at 6 months post intervention (T3).

Official Title
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The Effect of Goal Management Training for Adult Survivors of Childhood Leukemia and Non-Hodgkins Lymphoma With Neurocognitive Sequelae: A Randomized Controlled Trial

Conditions
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Childhood Non-Hodgkin Lymphoma, Childhood Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia

Intervention / Treatment
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* Behavioral: Goal Management Training (GMT)
* Behavioral: Brain Health Workshop (BHW)


Participation Criteria
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Eligibility Criteria
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The Norwegian Cancer Registry will identify participants based on the following criteria: Acute Lymphoblastic Leukaemia (ALL), Acute Myelogen Leukemia (AML), non Hodgkins Lymphoma diagnosed between 1980 - 2017 Age when diagnosed <18 år (0-17years) Age at survey 18-40 years Born between 1980 - 2004 Minimum five years (≥5) post ALL, AML, NHL diagnosis ALL, AML, NHL treatment at Oslo University Hospital and St. Olavs Hospital Inclusion Criteria Screening/baseline: Written informed consent ≥5 years from diagnosis Age 18-40 Without cancer recurrence the last five years Understand and speak Norwegian Additional inclusion criteria for the intervention: Experiencing executive dysfunction as determined by a semi-structured interview Cognitive capacity to engage with the training, and General Ability Index (GAI) Score ≥70 measured by Wechsler Intelligence Scale for Adults (WAIS-IV) Exclusion Criteria: Cancer recurrence within the last five years A history of premorbid Central Nervous System (CNS) injury or disease (e.g., Traumatic brain injury with noticeable cognitive changes, loss of consciousness or injury discovered on CT or MR) Pre-existing attention deficit hyperactivity disorder (ADHD) Motor or sensory damage impeding study participation A major psychiatric disease and/or ongoing substance abuse impeding study participation Present suicidal ideation Down syndrome

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Goal Management Training (GMT)<br>GMT will be administrated in a group-based format over 5 sessions (minimum three weeks between each session). Homework assignments between sessions are included. Following the fourth session, text messages reading Stop! (a key instruction in GMT) will be sent to all GMT participants every day to maximize adherence to training (approximately 12 per participant). Homework assignment will also include the logging of automatic thoughts and an examination of the relationship between situations, thoughts, and accompanying emotions. | Behavioral: Goal Management Training (GMT)<br>* The manual comprises an introduction to GMT for the survivors of ALL, and a detailed session structure incorporating cognitive and behavioral tasks. The GMT program involves teaching the participants about goals, attention slips and how to manage these, how to review and prioritize goals (e.g., Stop, Think, Organize, Plan), and how to keep goals in mind (e.g., using analogies such as the mental blackboard). Each session will follow the same general format; namely, facility-delivered presentations, flipchart discussions, group activities and homework.<br>|
| Active Comparator: Waitlist/Brain Health Workshop (BHW)<br>The adults participating in the control condition will approximately one year from waitlist, be offered a psycho-educative training program, the BHW, in groups aimed at providing a better understanding of cognitive sequelae after treatment for childhood ALL. BHW will be administrated in a group-based format over 5 sessions (minimum three weeks between each session). Homework assignments between sessions are included. Homework assignments between sessions are included. | Behavioral: Brain Health Workshop (BHW)<br>* BHW is a psycho-educative control condition, and is typically part of psycho-educative Acquired Brain Injury (ABI) rehabilitation programs, but adjusted for the ALL group of participants. The psycho-educative control condition BHW will be matched GMT for amount of training and therapist contact. Homework assignment and in-session tasks included readings, brain games, puzzles, and practical exercises such as logging sleep.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Behavior Rating Inventory of Executive Function, Adult (BRIEF-A) | The BRIEF-A self-report questionnaire consists of 75 items on which the patient's symptoms are rated on a 3-point Likert scale. The questionnaire provides a Global Executive Composite (GEC) score (range 75-225) and two index scores: the Behavioral Regulation Index (BRI) (range 30-90) and the Metacognitive Index (MI) (range 40-120). Nine subscales are also provided: Inhibit (range 8-24), Shift (range 6-18), Emotional control (range 10-30), Self-monitor (range 6-18), Initiate (range 8-24), Working memory (range 8-24), Plan/organize (range 10-30), Task monitor (range 6-18) and Organization of materials (range 8-24). Higher scores indicate more executive difficulties. Raw scores are transformed into t scores (M=50, SD=10). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conner's Continuous Performance Test (CPT-3) | The CPT 3 is a measure of inattention, impulsivity, sustained attention and vigilance. The test is computer based and lasts approximately 14 minutes. The participant is instructed to press the space bar/computer mouse when letters appear, but not when Xs appear on the screen. Higher scores reflect worse performance, and raw scores are converted to T-scores (M=50, SD=10). However, scores will be recoded so that higher scores equal better performance/lower scores equal worse performance. | 6 months | 
| The Color-Word Interference Test (CWI), from Delis Kaplan Executive Function System | The CWI is a measure of inhibition and cognitive flexibility. The test consists of four conditions; color naming (condition 1), word reading (condition 2), inhibition (condition 3) and inhibition switching (condition 4). Scores are computed for completion time (condition 1-4) and total errors (condition 3 and 4). Higher scores reflect better performance, and raw scores are converted to scaled scores (M=10, SD=3). | 6 months | 
| The Trail Making Test (TMT): from Delis Kaplan Executive Function System | The TMT from Delis Kaplan Executive Function System is a measure of flexibility/shifting. The primary measure is condition 4 where the participant is asked to shift between number and letter sequencing. The test also measures the basic abilities of visual scanning (condition 1), number- and letter sequencing combined with drawing a line (condition 2 and 3) and motor pace (Condition 5). Scores reflect completion time and raw scores are converted to scaled scores (M=10, SD=3). Higher scores reflect better performance. | 6 months | 
| California Verbal Learning Test (CVLT II) | The CVLT II a measure of verbal learning and memory. Participants are asked to recall words from list A, both with and without an interruption list B. There are three types of conditions; the participant is asked to freely recall items (free recall), to recall after a cue is presented (cued recall) and to recognize previously presented words (recognition condition). Both short and long delay is measured. Raw scores are converted to Z-scores (M=0, SD=1) and T-scores (M=50, SD=10). Higher scores reflect better performance, except for error measures. For T2 (14 days) follow up, CVLT II Alternative Form will be used. | 6 months | 
| Wisconsin Card Sorting Test (WCST-64) | The WCST-64 is a measure of abstract thinking and set-shifting/ mental flexibility. The participant is instructed to sort cards according to varying principles. A computer-based version will be employed. Raw scores are converted to T-scores (M=50, SD=10) and higher scores reflect better performance. | 6 months | 
| The Hotel Task | The Hotel Task is a measure of executive components: planning, organization, self-monitoring and cognitive flexibility. The participant is asked to try out as many as possible of five tasks within a relatively short (15 minutes) time period. Raw scores are computed. Higher scores reflect better performance, except for deviation of optimal time use. The test has been demonstrated to have high ecological validity and ability to detect frontal lobe dysfunction. | 6 months | 
| The Dysexecutive Questionnaire (DEX - self-report) | The DEX - self-report is a measure of everyday problems with executive function. The questionnaire consists of 20 items with a 5-point Likert scale where the respondent is asked to rate the frequency of cognitive difficulties from 0 (never) to 4 (very often). A higher total score reflects worse executive functioning. | 6 months | 
| Wechsler Adult Intelligent Scale-IV - Fourth Edition (WAIS-IV) | The subtests: Digit span, letter-number sequencing performance will be used as a measure of Verbal working memory/attention (Working memory index). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult survivor, Childhood, Cognitive Remediation, Executive Function, Cognitive Rehabilitation, Cognitive Training, Metacognitive, Late effects, Goal Management Training, Cancer