<p><strong>BACKGROUND: </strong>Adolescents and young adults (AYAs) with cancer demonstrate suboptimal oral chemotherapy adherence, increasing their risk of cancer relapse. It is unclear how everyday time-varying contextual factors (eg, mood) affect their adherence, stalling the development of personalized mobile health (mHealth) interventions. Poor engagement is also a challenge across mHealth trials; an effective adherence intervention must be engaging to promote uptake.</p>

<p><strong>OBJECTIVE: </strong>This protocol aims to determine the temporal associations between daily contextual factors and 6-mercaptopurine (6-MP) adherence and explore the proximal impact of various engagement strategies on ecological momentary assessment survey completion.</p>

<p><strong>METHODS: </strong>At the Children's Hospital of Philadelphia, AYAs with acute lymphoblastic leukemia or lymphoma who are prescribed prolonged maintenance chemotherapy that includes daily oral 6-MP are eligible, along with their matched caregivers. Participants will use an ecological momentary assessment app called ADAPTS (Adherence Assessments and Personalized Timely Support)-a version of an open-source app that was modified for AYAs with cancer through a user-centered process-and complete surveys in bursts over 6 months. Theory-informed engagement strategies will be microrandomized to estimate the causal effects on proximal survey completion.</p>

<p><strong>RESULTS: </strong>With funding from the National Cancer Institute and institutional review board approval, of the proposed 30 AYA-caregiver dyads, 60% (18/30) have been enrolled; of the 18 enrolled, 15 (83%) have completed the study so far.</p>

<p><strong>CONCLUSIONS: </strong>This protocol represents an important first step toward prescreening tailoring variables and engagement components for a just-in-time adaptive intervention designed to promote both 6-MP adherence and mHealth engagement.</p>

<p><strong>INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): </strong>DERR1-10.2196/32789.</p>