Background: Oral mucositis (OM) is a serious complication of cancer treatments characterized by erythema and ulcerations of the mouth. Consequences of OM include pain, diminished functionality, and infections leading to decreased quality of life and discontinuity in therapy. About 20-40% of patients receiving chemotherapy develop OM within 7 days of treatment initiation. Current clinical guidelines recommend prophylactic oral care, cryotherapy, KGF-1, palifermin, and photobiomodulation to prevent OM in specific patient groups. Benzydamine is approved for the prevention of OM in head and neck cancer patients receiving radiotherapy or radio-chemotherapy but has not been well studied for chemotherapy alone. The effectiveness of oral topical treatments is limited by dilution in the saliva and swallowing shortening the duration of their action. Bocaliner is a novel medical device that is hypothesized to enhance the effects of treatments by prolonging the oral retention of topical therapies within the oral cavity. Methods: The Study for the Prevention of Oral Mucositis (SPOM) is a randomized controlled Phase I/II trial that aims to evaluate the efficacy of two different tools (benzydamine mouthwash and Bocaliner) in reducing the incidence and severity of OM in patients undergoing systemic chemotherapy (NCT05338398). A total of 100 adult patients with hematologic malignancies undergoing chemotherapy in a centralized hematology center in Armenia will be randomized into two different treatment groups: saline mouthwash and benzydamine mouthwash (0.15%, 120mL) 3-5 times a day for a total of two weeks. Half of the patients within each group will also randomly receive Bocaliner, which will be placed inside of their mouth immediately after the application of the mouthwash for 20 minutes. Block randomization will be applied with 4 patients per block with 1:1 randomization based on gender, Bocaliner use, and mouthwash type. The primary endpoint is the difference in OM incidence measured by the WHO Oral Toxicity Scale. The secondary endpoints are differences in OM symptoms evaluated using a modified version of the PROMS questionnaire. Safety and tolerability of the medical device will be determined for the Phase I component of the study based on responses to standardized tryout (Day 0) and follow-up questionnaires (Day 14). Other outcomes include the duration and severity of OM. Statistical analysis will explore further clinically meaningful associations between patient data, received therapies, and outcomes. Forty-two patients have already completed the study, while the enrollment of other participants continues and is planned to be completed by the end of 2023. Clinical trial information: NCT05338398.