Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Nervous System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Brain Neoplasms

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Central Nervous System Stimulants

All Drugs and Chemicals

Cardiotonic Agents

Methylphenidate

Dopamine

Dopamine Uptake Inhibitors

Dopamine Agents

Neurotransmitter Agents

Please see detailed description for dosing information and study design.

Heather M Conklin

Children surviving some types of cancer have a higher risk of developing learning problems after cancer treatment than do children who have not had cancer or its treatment. Cancer treatment may cause problems with learning, attention, and memory. The purpose of this study is to identify brain changes that may underlie learning problems in cancer survivors and investigate whether methylphenidate (a stimulant medication) may reduce these problems.

Subjects who have had treatment for acute lymphoblastic leukemia (ALL) or a brain tumor will be asked to take part in this research study. Siblings of some subjects will also be asked to take part, so that their results can be compared with those of children who have had cancer treatment. We hypothesize that children receiving more aggressive therapy will have lower white matter brain volumes and these volumes will be significantly lower than age-matched siblings. We also hypothesize that children who take methylphenidate will show improvements on teacher and parent report measures of attention and social skills.

This study is a multi-phase, multi-site methylphenidate (MPH) trial in childhood cancer survivors. Study participants that meet inclusion and exclusion criteria are screened to ensure that they have adequate global cognitive functioning (IQ \> 50) and have academic and attention difficulties that might be managed with MPH. Following the screening phase, qualifying participants take part in a two-day, in-clinic, double-blind, cross-over trial during which they receive MPH (0.6 mg/kg; maximum dose, 20 mg) and placebo (inert substance) in a randomly assigned order. Patients who do not have a significant adverse reaction during the two-day trial go on to participate in a randomized, double-blind, placebo-controlled, three-week home cross-over trial consisting of placebo, low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). Patients are then selected for participation in a 12-month open-label MPH trial if they show improvement over placebo on a parent and/or teacher rating of attention during the three-week home cross-over trial. The 12-month open-label MPH trial includes individually titrated MPH dosing to maximize clinical benefit, monthly monitoring of side effects and regular acquisition of parent and teacher ratings of attention and behavior. Laboratory measures of intellectual function, attention and memory are conducted at the end of the 12-month trial.

Learning Impairments Among Survivors of Childhood Cancer

To compare the white matter volume of patients with those of sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

To compare the white matter volume of Acute Lymphoblastic Leukemia (ALL) patients with those of patients with malignant brain tumors using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

To compare the white matter volume of patients by treatment intensity groups (mild, moderate, and high) and sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Methylphenidate (MPH) Home Maintenance Phase(baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

The Social Skills Rating System- Parent Version (SSRS-P) is a parent rating scale of social behaviors in reference to typically developing children. Thirty eight questions are rated 0 (Never) to 3 (very often). The social skills score is norm-referenced with a mean of 100±15 where a higher score is indicative of better skills. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Reading Composite consists of Basic Reading (single word reading) and Reading Comprehension. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Spelling score assesses the child's ability to spell words to dictation. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Math Composite score assesses the child's ability to solve calculation problems (Numerical Operations) and solve applied, word problems (Math Reasoning). Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were done weekly during the 3-week Home Crossover Period with the best response being used as the measurement for the test.

The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Omission errors are the raw score for the number of targets presented where the subject did not respond. Accordingly, the range for this variable is 0-54 with a higher score indicative of worse performance or problems with sustained attention.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Commission errors are the raw score for the numbers of nontargets presented where the subject incorrectly responded. Accordingly, the range for this variable is 0-6 with a higher score indicative of worse performance or impulsivity.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Hit reaction time is average reaction time in milliseconds for all correct responses when targets were presented. There is no pre-defined range for reaction time; higher score is indicative of slower processing speed.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. D' is a measure of sensitivity of a person to the signal or target; a higher score is indicative of better performance or better sustained attention. D' was calculated as z(hit) - z(commission). Z-scores were calculated using the NORMSINV function in Microsoft Excel.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. β is a measure of response tendency; higher scores indicate a more conservative response pattern. β was calculated using the formula = -d'\*.5\*(NORMSINV(hits)-NORMSINV(false alarms)). In the case where the false alarm rate = 0 or the hit rate = 1.0, we used the standard correction of 1/2N and 1- 1/2N, respectively.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Trials 1-5 have a mean T Score of 50 and Standard Deviation of 10.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Short Delay Free Recall has a mean of 0 and a standard deviation of 1.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Long Delay Free Recall has a mean of 0 and a standard deviation of 1.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Word Naming Time have a mean of 50 and a standard deviation of 10.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Color Naming Time have a mean of 50 and a standard deviation of 10.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Ink Color Naming Time have a mean of 50 and a standard deviation of 10.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Interference Score have a mean of 50 and a standard deviation of 10.

National Cancer Institute (NCI)

St. Jude Children's Research Hospital

Intensity of prior Central Nervous System radiation therapy was considered mild.

Mild

Intensity of prior Central Nervous System radiation therapy was considered moderate.

Moderate

Intensity of prior Central Nervous System radiation therapy was considered high.

High

Patients not randomized for the MPH in Lab Phase

Not Randomized-In Lab Phase

Group M/P (patients receive oral Methylphenidate (MPH) and then an oral placebo)

Group M/P

Group P/M (patients receive oral placebo and ten Methylphenidate (MPH))

Group P/M

Patients who completed the MPH in Lab Phase but were not randomized for the MPH Cross Over Phase

Not Randomized-Cross Over

The PLM group received a placebo on week one, low dose Methylphenidate (MPH) on week two, and a moderate dose of Methylphenidate (MPH) on week three.

Placebo/Low Dose/Moderate Dose (PLM)

The PML group received a placebo on week one, moderate dose Methylphenidate (MPH) on week two, and a lose dose of Methylphenidate (MPH) on week three.

Placebo/Moderate Dose/Low Dose (PML)

The LMP group received a low dose of Methylphenidate (MPH) on week one, a moderate dose of Methylphenidate (MPH) on week two, and a placebo on week three.

Low Dose/Moderate Dose/ Placebo (LMP)

The LPM group received a low dose of Methylphenidate (MPH) on week one, a placebo on week two, and a moderate dose of Methylphenidate (MPH) on week three.

Low Dose/Placebo/Moderate Dose (LPM)

The MLP group received a moderate dose of Methylphenidate (MPH) on week one, a low dose of Methylphenidate (MPH) on week two, and a placebo on week three.

Moderate Dose/Low Dose/Placebo (MLP)

The MPL group received a moderate dose of Methylphenidate (MPH) on week one, a placebo on week two, and a low dose of Methylphenidate (MPH) on week three.

Moderate Dose/Placebo/Low Dose (MPL)

Patients who completed the MPH Cross Over Phase but chose to decline participation in the Home Maintenance Phase.

Declined Home Maintenance Phase

Methylphenidate (MPH) was administered for 12 months during the duration of the Home Maintenance Phase.

Home Maintenance Phase

Total

< 4 years of age

≥ 4 years of age

Age, Customized

Sex: Female, Male

Acute Lymphoblastic Leukemia (ALL)

Brain Tumors (BT)

Disease Group

Heather Conklin PhD

Patients

Siblings

Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images. 67 of the 91 sibling controls had evaluable MRI images.

Brain White Matter Volume for Patients Versus Sibling Controls

Patients with Acute Lymphoblastic Leukemia (ALL) who had evaluable MRIs.

Patients With ALL

Patients with brain tumors who had evaluable MRIs.

Patients With Brain Tumors

Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images.

Brain White Matter Volume for Patients With Acute Lymphoblastic Leukemia Versus Brain Tumors

The sibling control group received no radiation therapy.

Mildly intense central nervous system therapy (systemic and/or intrathecal chemotherapy only)

Mild Treatment Intensity

Moderately intense central nervous system therapy (\<= 24 Gy CRT with or without systemic and/or intrathecal chemotherapy).

Moderate Treatment Intensity

High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.

High Treatment Intensity

Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images. 67 of the 91 sibling controls had an evaluable MRI image.

Brain White Matter Volume for Treatment Intensity Groups and Sibling Controls

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: ADHD T Questionnaire and 59 were screen at completion. 47 patients were screened at both the beginning and end of the home maintenance phase.

Overall

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: ADHD T Score Questionnaire and 59 were screen at completion. 47 patients were analyzed.

Change From Methylphenidate (MPH) Home Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: ADHD T Score)

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: Cognitive Problem T Score Questionnaire and 59 were screen at completion. 47 patients were screened at both the beginning and end of the home maintenance phase.

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: ADHD T Score Questionnaire and 59 were screened at completion. 47 patients were analyzed.

Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: Cognitive Problem T Score)

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: ADHD T Questionnaire and 68 were screen at completion. 68 patients were screened at both the beginning and end of the home maintenance phase.

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: ADHD T Score Questionnaire and 68 were screen at completion. 68 patients were analyzed.

Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score)

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: Cognitive Problem T Questionnaire and 68 were screen at completion. 68 patients were screened at both the beginning and end of the home maintenance phase.

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: Cognitive Problem T Score Questionnaire and 68 were screened at completion. 68 patients were analyzed.

Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conner's Parent Rating Scale (CPRS: Cognitive Problem T Score)

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Social Skills Rating System and 68 were screened at completion. 68 patients were screened at both the beginning and end of the home maintenance phase.

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Social Skills Rating System (SSRS-P) and 68 were screened at completion. 68 patients were analyzed.

Change From Maintenance Phase Baseline to Completion of Phase as Measured by Social Skill Rating System (SSRS-P)

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the WIAT Reading: Composite Standard Score System and 68 were screened at completion. 68 patients were screened at both the beginning and end of the home maintenance phase.

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) REading: Composite Standard Score questionnaire and 68 were screened at completion. 68 patients were analyzed.

Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Reading: Composite Standard Score

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the WIAT Spelling: Standard Score System and 68 were screened at completion. 68 patients were screened at both the beginning and end of the home maintenance phase.

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score System and 68 were screened at completion. 68 patients were analyzed.

Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score

118 patients began the home maintenance phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the WIAT Math: Composite Standard Score System and 68 were screened at completion. 68 patients were screened at both the beginning and end of the home maintenance phase.

118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score System. 68 were screened at completion. 68 patients were analyzed.

Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score

Oppositional T Score

Cognitive Problems/Inattention T Score

Hyperactivity T Score

Adhd T Score

Patients assigned to the placebo group were randomly assigned to receive one of two arms: Group PLM received placebo during week one, low dose during week 2, and moderate dose during week 3; Group PML received placebo during week one, moderate dose during week 2, and low dose during week 3.

Placebo

Patients assigned to the Low Dose group were randomly assigned to receive one of two arms: Group LMP received low dose during week one, moderate dose during week 2, and placebo during week 3; Group LPM received low dose during week one, placebo during week 2, and moderate dose during week 3.

Low Dose

Patients assigned to the Moderate Dose group were randomly assigned to receive one of two arms: Group MLP received moderate dose during week one, low dose during week 2, and placebo during week 3; Group MPL received moderate dose during week one, placebo during week 2, and low dose during week 3.

Moderate Dose

There were 122 patients treated in the home crossover period. Some patients had missing treatments and outcome assessments. A crossover design was used for better efficiency of test and better precision of estimation.

Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase.

Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.

Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.

Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.

122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Cognitive Problem/Inattention Scale.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Hyperactivity Scale.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) ADHD Index.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Cognitive Problem/Inattention Scale.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Hyperactivity Scale.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) ADHD Index.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Social Skill.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Problem Behavior.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Social Skill.

Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.

Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Problem Behavior.

Of the 469 screened patients, 259 did not qualify for further medication phases, 75 qualified but refused to participate and 1 did not show for a scheduled appointment, leaving 134 patients to participate in the two-day Methylphenidate (MPH) In-Lab Phase. 67 patients were assigned to the Group M/P sequence and 67 were assigned to the Group P/M sequence. Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We tested the difference in effects of MPH and placebo not the difference of two sequence groups.

MPH (Methylphenidate)

MPH Versus Placebo

A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Omission Errors.

Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Commission Errors.

Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Hit Reaction Time.

Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for d' (Sensitivity).

Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Beta (Risk Taking).

Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) Over Five Learning Trials.

Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Short Delay Free Recall.

Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Long Delay Free Recall.

Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Word Naming Time.

Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Color Naming Time.

Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Ink Color Naming Time.

Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Interference Score.

Intensity of prior CNS Therapy (systemic and/or intrathecal chemotherapy only)classified as mild.

Mild Intensity

Intensity of prior CNS Therapy (\< 24 Gy CRT with or without systemic and/or intrathecal chemotherapy)classified as moderate.

Moderate Intensity

Intensity of prior CNS Therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy) classified as high.

High Intensity

Of the 469 screened patients, 259 did not qualify for further medication phases, 75 qualified but refused to participate and 1 did not show for a scheduled appointment, leaving 134 patients to participate in the two-day Methylphenidate (MPH) In-Lab Phase.

Screened/Didn't Qualify for Methylphenidate (MPH) In-Lab Phase

Group M/P (patients received oral Methylphenidate (MPH) and then an oral placebo)

Spots Global Cancer Trial Database for brain tumor, acute lymphoblastic leukemia, methylphenidate, cognitive late effects