A Phase Ib Clinical Trial of PV701, a Milk-Derived Protein Extract, for the Prevention and Treatment of Oral Mucositis in Patients Undergoing High-Dose BEAM Chemotherapy

Despite the best available agents to prevent mucositis, most patients receiving high-dose chemoradiotherapy regimens experience severe mucositis, and new therapies are needed. In this study, we evaluated the safety and tolerability of a milk-derived growth factor extract (PV701 mouthwash) intended to prevent oral mucositis (OM) after carmustine, etoposide, cytosine arabinoside, and melphalan (BEAM) chemotherapy. PV701 mouthwash (15 mL × 13.5 mg/mL) was administered 6 times a day for 12 days, from day −6 to day +5, to patients with lymphoma, who were given BEAM on day −6 to day −2, with autologous stem cells infused on day 0. Dose de-escalation of PV701 was planned if dose-limiting toxicities occurred. The severity and duration of OM, the duration of enteral/parenteral feeding, the requirement for intravenous opiates, and admission to intensive care were recorded. Outcomes were also compared with those of historical control patients. Nine patients received PV701 13.5 mg/mL. PV701 was well tolerated, and no dose-limiting toxicities were observed. Compared with 89 historical controls, the 9 PV701-treated patients had significantly less frequent grade 2 or 3 OM (P = .0006) and had grade ≥3 OM for an estimated 5 fewer days (P = .0003). There was a reduction in the need for enteral/parenteral feeding (P = .012), its duration (P = .010), and its frequency (P = .022) and in the duration of intravenous opiates (P = .0006). We conclude that PV701 mouthwash is readily administered with minimal side effects at a dose of 1215 mg/d, and further investigation of this agent is warranted.