A Prospective, Randomized, Comparative Trial of Cryotherapy Versus Caphosol Versus Saline Solution Mouth Washes for the Prevention of Oral Mucositis in Patients With Multiple Myeloma Undergoing Hematopoietic Stem Cell Transplantation.

INVESTIGATIONAL PLAN Study design This is a single center, prospective, randomized, comparative study to evaluate the effectiveness of saline solution, cryotherapy and Caphosol mouth rinse for the prevention of oral mucositis. Multiple myeloma (MM) patients who are eligible for an autologous hematopoietic stem cell transplantation (HSCT) and are at least 18 years of age will be screened to enroll approximately 165 patients. During the study patients will receive prophylactic fluconazole, acyclovir and antibiotics as appropriate (standard of care). Systemic analgesia will be given for the control of oral pain resulting from mucositis to any of the groups as required. All treatment groups will receive identical oral hygiene care instructions. Treatments not permitted in the study include GM-CSF, palifermin (Kepivance) or other mouthwash and oral coating agents such as Gelclair during the study period to reduce confounding factors.

All patients will receive high-dose melphalan 100 mg /m2/day for 2 days (day -2 and -1) as conditioning regimen followed by autologous HSCT (day 0). After informed consent and completion of screening period, patients will be randomized to any of the three arms. Randomization will be stratified by patient age, sex, and performance status. Patients will be monitored daily post-conditioning until the patients are discharge from the hospital or admitted into an intensive care unit. The oral mucosa will be examined by trained study staff. Oral mucositis will be assessed daily until hospital discharge, after the first day of melphalan, for patients who do not develop oral mucositis or until the oral mucositis resolves for patients who develop any mucositis to a maximum of 30 days. The oral mucositis will be assessed using the World Health Organization (WHO) Mucositis Scale, the Oral Mucositis Assessment Scale (OMAS) and the National Cancer Institute (NCI) Common Toxicity Criteria. At the same time the mucositis-related pain (mouth pain) will be evaluated based on the Wong-Baker Faces Pain Rating Scale and the Numeric Rating Scale (Appendix B). Questionnaire for Patient-reported Oral Mucositis Symptoms (PROMS) Scale will be obtained at screening and every day after first day of melphalan until end of study. All patients will receive the Program's standard oral hygiene instructions prior to initiation of study.

ARM #1:

Standard of care for prevention and management of oral mucositis (0.9% Sodium Chloride irrigation solution): Patients randomized to this group will be instructed to rinse their mouths twice, with 1 ounce (30 ml) of room temperature 0.9% NaCl (normal saline), 4 times daily after admission and until end of study.

ARM #2: