Purpose <p>Around 40% of patients undergoing systemic chemotherapy develop oral mucositis (OM), a major cause of morbidity in cancer patients. There are only a few options for preventing and treating OM. This study examines the tolerability of a novel oral device (Bocaliner™), designed to enhance the effects of oral topical therapies, in patients with hematologic malignancies receiving chemotherapy.</p> Methods <p>Data from phase 1/phase 2 randomized controlled trial SPOM (Study for the Prevention of Oral Mucositis) was analyzed. Patients from the Yeolyan Hematology and Oncology Center (Yerevan, Armenia) were randomized into two groups: benzydamine or saline mouthwash. Half of the patients in each study group were randomly assigned to Bocaliner™. Tolerability and safety questionnaires on days 1 and 14 of chemotherapy were completed.</p> Results <p>Twenty-eight patients (mean age of 49 years; 50% female) received oral devices and completed the study. On the tryout of the device, 22 (78.6%) patients reported tolerating it well, and six (21.4%) reported some discomfort. After 14 days, 15 patients (35.7%) reported benefit from the use, with six (21.4%) of patients stating the device helped to reduce pain, four (14.3%) indicating that it helped them to eat, and five (17.8%) claiming both. Adverse events included discomfort (<i>n</i> = 2, 7.1%), pain around the cheekbone (<i>n</i> = 3, 10.7%), nausea (<i>n</i> = 2, 7.1%), and increased salivation (<i>n</i> = 1, 3.6%); none of these led to discontinuation of the use. Eighteen (64%) participants said they would use the device again. OM developed in five patients (17.8%).</p> Conclusions <p>The use of a new medical device designed to enhance oral topical medications in combination with oral topical therapy is well tolerated among patients with hematologic malignancies on chemotherapy.</p> <p>Trial registration.</p> <p>ClinicalTrials.gov registry ID: <i>NCT05338398</i> (Date of registry: April 15, 2022).</p>