DESCRIPTION (provided by applicant): Targeted therapies are a new generation of drugs designed to interfere with molecular targets critical for tumor growth and progression. One of the first and most successful examples is the oral medication imatinib developed for chronic myelogenous leukemia (CML). Although imatinib and similar medications are much better tolerated than regimens they replaced, they still possess side effects that are bothersome to patients, interfere with quality of life, and contribute to problems with adherence. Since treatment typically continues on a daily basis for many years and may be life-long, effective management of side effects is critically important. Recent studies show that fatigue is the most common and bothersome symptom identified by CML patients being treated with oral targeted therapy. The proposed research represents the first systematic attempt to address the problem of targeted therapy-related fatigue (TTF). Toward this end, it builds on previous research showing that a form of cognitive behavior therapy (CBT) based on a precipitating-perpetuating model of symptom evolution is highly effective against fatigue in cancer patients with no clinical evidence of disease who have completed treatment (i.e., post-cancer fatigue or PCF). Accordingly, in collaboration with its developers, we will adapt CBT-PCF, an intervention based on the precipitating-perpetuating model for fatigued patients who completed treatment, to develop CBT-TTF, an intervention based on a revised precipitating-exacerbating model for fatigued patients on maintenance targeted therapy. Adopting the tailored modular approach of the original intervention, we will first conduct iterative qualitative research with fatigued CML patients and CML care providers to determine which CBT-PCF modules to retain and adapt and to identify potential new modules to develop based on the conceptual model. The adaptation also involves moving from clinic-based delivery to Internet-assisted delivery using video telephony and tablet computer technology (FaceTime using iPads) in order to minimize travel burden, maximize convenience, and foster greater dissemination potential. Once developed, CBT-TTF will be evaluated with fatigued CML patients on oral targeted therapy for feasibility, acceptability and potential efficacy relative to usual care only in a small-scale randomized controlled trial. The specific aims are to: 1) develop an Internet-assisted form of CBT for TTF (CBT-TTF) using as a foundation an empirically-supported form of CBT effective against post-treatment cancer-related fatigue; 2) evaluate CBT-TTF and related methods for feasibility and acceptability; 3) explore the efficacy of CBT-TTF in reducing fatigue (primary outcome); and 4) explore the efficacy of CBT-TTF in improving quality of life and oral medication adherence (secondary outcomes). Successful completion of this research will provide a strong foundation for a larger multi-center clinical trial expected to yield a highly effective and readily disseminale intervention that addresses a major treatment consequence in the growing population of patients for whom target therapies are transforming cancer from a life-threatening illness to a chronic illness.