Trial Information

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:

Cryotherapy (ice chips): Patients randomized to this group, on day -2 and -1, will be
instructed to place approximately 1 ounce of crushed ice in their mouths 15 minutes prior to
the initiation of melphalan infusion. The ice will be allowed to melt and should be
replenish as soon as it had completely melted. Patients will be instructed to continue this
procedure during the melphalan infusion and for 90 minutes after the end of the infusion.
After patients are done with the cryotherapy they will follow the standard of care for
prevention and management of oral mucositis until the end of the study.

ARM #3:

Calcium phosphate (Caphosol) Ca2+/PO43- mouth rinse: Patients randomized to this group will
be instructed to rinse their mouths with Caphosol 4 times daily after admission and until
end of study.

All patients, who develop oral mucositis pain, will follow the Bone Marrow Transplant
Program standard of care to control the pain in patients undergoing HDC and autologous HSCT.
The Program standard care for oral mucositis pain consists in the use of triple mix
solution (lidocaine, Maalox, and diphenhydramine) and analgesics. Patients in the Caphosol
rinse arm who develop severe mucositis will be instructed to rinse up to 10 times a day.