Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for ALL

This study is a double-blind, placebo-controlled, parallel group trial of atomoxetine (1.8 mg/kg) for the management of chemotherapy-related acquired attentional disorders in children who have survived Acute Lymphocytic Leukemia. Atomoxetine will produce a favorable impact on ADHD symptoms in children with chemo-related acquired attentional disorders.

The primary objective of this study is to assess the safety, tolerability and efficacy of atomoxetine as determined by the change in the ADHD-RS-IV Total score compared to placebo in the symptomatic treatment of patients diagnosed with Attention-Deficit/Hyperactivity Disorder (by DSM-IV ADHD-NOS criteria) occurring as a neuropsychological late-effect of chemotherapy used to treat Acute Lymphocytic Leukemia (ALL).

The secondary objectives are:

1. to assess the effect of once daily (AM) dosing of atomoxetine (1.8mg/kg) compared to placebo on ADHD symptoms as measured by:

   * ADHD-RS Total score inclusive of subtypes for inattention, hyperactivity and combined subtypes.
   * Clinical Global Impression-ADHD
2. to evaluate the safety and tolerability of atomoxetine compared with placebo based on treatment-emergent adverse events (AEs), laboratory tests, vital signs, physical examinations, and ECGs.

Eligibility Criteria:
Inclusion Criteria:

* Ages 6-18 years
* Must have successfully completed treatment for ALL and are currently 1-year "disease free" as judged by the investigators.
* Must meet DSM-IV criteria for "ADHD-NOS.( Attachment A) The attention deficit symptoms have been precipitated by chemotherapy-related neurological injury. Therefore, the DSM-IV category is ADHD-NOS.
* Must have an Investigator-completed ADHD-RS total and/or subscale score of ≥1.5 standard deviations above age/gender norm.
* Laboratory results, including chemistries, hematology, and urinalysis do not demonstrate clinically significant abnormalities.
* ECG demonstrates no clinically significant abnormalities
* Educational level and degree of understanding of the patient and their parents permit suitable communication between the investigators and study coordinators.
* Subjects and parents are judged to be reliable to keep appointments.
* Must be able to swallow tablets.
* Must have demonstrated compliance during their chemotherapy program.
* Must weigh \> 20 kg.

Exclusion Criteria:

* Have relapsed or are having re-occurring symptoms/signs of ALL.
* Have had substantial exposure to radiation therapy (\>2000: cGy) since high dose radiation treatment is associated with neurocognitive deficits or be "treatment resistant" pharmacologically.
* Past exposure to atomoxetine.
* ADHD symptoms or treatment prior to the diagnosis of ALL
* Documented bipolar disorder, psychosis, affective disorder.
* Female subjects who are pregnant or breastfeeding.
* Suicide risk.
* Seizure disorders (except history of febrile seizures).
* Histories of multiple drug allergies.
* Histories of alcohol or substance abuse.
* Prior or current medical conditions that, in the opinion of the investigators, could be exacerbated by atomoxetine.
* Sympathomimetic overactivity such as catecholamine secreting tumor.
* Use of MAOI medications.
* Have taken psychostimulants one week prior to randomization.
* Current or past history of hypertension.