2025 Southeastern Residency Conference

Title: Randomized, Blinded Study of Olanzapine 2.5mg versus 5mg in Quadruplet Prophylaxis of Nausea/Vomiting after High-Dose Melphalan for Autologous Transplantation (The FONDO-LOW Trial)


Authors: Hanh Tran, E. Behren Ketchum, Vamsi Kota, Amber Clemmons


Objective: This study aims to determine the optimal dose of olanzapine when added to triplet prophylaxis in preventing CINV while minimizing the risk of daytime sedation after high-dose melphalan for patients with multiple myeloma receiving auto-HCT.


Self Assessment Question: In the FONDO-LOW study, subjects were assessed for emesis episodes, nausea severity, and sedation severity over five consecutive days. Each day, they rated their nausea and sedation severity using a 4-point scale based on their experiences in the past 24 hours. (True)


Background: Chemotherapy-induced nausea and vomiting (CINV) is a common and difficult to manage side effect. Olanzapine is an FDA-approved atypical antipsychotic that blocks multiple neuronal receptors involved in nausea/vomiting pathways. The FOND-O trial conducted at our institution by Clemmons and colleagues previously determined that adding olanzapine 10 mg to triplet prophylaxis (fosaprepitant, ondansetron, dexamethasone) improved CINV for patients undergoing high-dose chemotherapy for autologous stem cell transplantation (auto-HCT). Results from that trial led to the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines offering the olanzapine-based quadruplet regimen as an option for this population. Despite the high efficacy, several studies have shown that the 10 mg olanzapine dose may be associated with substantial daytime somnolence. Current NCCN guidelines recommend low-dose olanzapine of 5 mg or 2.5 mg if 10 mg or 5 mg, respectively, causes excessive sedation. Additionally, many transplant centers endorse utilizing lower doses to avoid the sedating effect of olanzapine. Despite the use of lower doses in practice, no publications have evaluated an optimal dose of olanzapine in reducing CINV and minimizing daytime sedation when added to standard triplet therapy for patients receiving high-dose melphalan for auto-HCT.


Methods: This is a single-center, prospective, randomized, double-blind study. Inclusion criteria are adult patients 18 years and older who receive high-dose melphalan 140-200 mg/m2 prior to auto-HCT. Patients will be randomized to receive encapsulated olanzapine 5 mg or 2.5 mg tablet orally on the day of high-dose melphalan and for three additional days post-chemotherapy in addition to standard triplet antiemetic prophylaxis consisting of an NK-1 receptor antagonist, ondansetron, and dexamethasone. Primary endpoint is percentage of patients achieving overall CINV complete response (CR), defined as no emesis and no more than mild nausea on 0-4 scale (0-none, 1-mild, 2-moderate, 3-severe), between the two olanzapine dosing groups. Secondary endpoints are complete protection (CR plus no breakthrough antiemetic use), total number of emetic episodes and breakthrough antiemetic doses, rate of study drug discontinuation, and incidence of no more than mild daytime sedation per patient report on the 4-point scale (none to severe). All outcomes will be reported in acute (chemotherapy day), delayed (four days after chemotherapy), and overall 5-day assessment periods. With an 80% power alpha of 0.05, 86 patients recruited for each arm to detect a 10% difference between groups. Hence, a total of 172 patients will be accrued for 3 years. Descriptive statistics are utilized to analyze patient demographics whereas Chi-square and t-test are used for primary and secondary outcomes.


Results: In Progress


Conclusion: In Progress