Topical Phenylephrine Solution in Preventing Oral Mucosa in Bone Marrow Transplant Patients Receiving Cyclophosphamide and Total Body Radiation Therapy

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of phenylephrine (topical phenylephrine solution)
applied topically to the oral mucosa of bone marrow transplant patients treated with
cyclophosphamide plus total body irradiation.

II. To determine the maximum tolerated dose (MTD) and recommended phase II dose of
phenylephrine applied topically to the oral mucosa of bone marrow transplant patients treated
with cyclophosphamide plus total body irradiation.

III. To evaluate the efficacy of phenylephrine applied topically to the oral mucosa in
preventing and/or decreasing severity of oral mucositis in bone marrow transplant patients
treated with cyclophosphamide plus total body irradiation.

OUTLINE: This is a phase I, dose-escalation study of topical phenylephrine solution followed
by a phase II study.

Patients undergoing a cyclophosphamide and total body irradiation regimen receive topical
phenylephrine solution via spray to the oral mucosa 15-20 minutes prior to each
cyclophosphamide infusion, 25-30 minutes after the beginning of each cyclophosphamide
infusion, and 15-20 minutes prior to each radiation treatment.

After completion of study treatment, patients are followed up weekly for 2 weeks and then at
3 months.

Inclusion Criteria:

- Be planning to receive a conditioning regimen for stem cell transplant (SCT)
consisting of cyclophosphamide and total body irradiation and must meet inclusion
criteria for SCT which include:

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
2 or less

- Patients must have no evidence of active infections at the time of transplantation

- Patients must be human immunodeficiency virus (HIV) non-reactive

- Females of childbearing potential must not be pregnant or breastfeeding on admission
for conditioning for SCT and a pregnancy test will be required for all females of
child-bearing potential

- Patients must have a pre-transplant multi-organ assessment with the following outcome:

- A resting ejection fraction of 50% or greater which increases with exercise as
demonstrated by resting/exercise multigated acquisition (MUGA)

- A forced expiratory volume in one second (FEV1) of 60% or greater, a diffusion
capacity of 50% or greater, and a oxygen partial pressure (PO2) of 80 mm mercury (Hg)
or greater on pulmonary function testing

- A serum creatinine of equal or less than 2.0mg/Dl and a creatinine clearance of 50
mL/min or greater on 24 hour urine collection

- A total bilirubin of less than 2.5 mg/dL, unless these values are due to underlying
hematologic malignancy

- An aspartate aminotransferase (AST) less than 2 times the upper limit of normal,
unless these values are due to underlying hematologic malignancy

- Be able to tolerate topical application of phenylephrine to the oral mucosa

- All patients must sign a written informed consent

Exclusion Criteria:

- Open or unhealed wounds or ulcers in the oral cavity

- Current use or use within past two weeks of an monoamine oxidase inhibitor (MAOI)

- Primary or secondary tumor in the oral cavity

- Known allergy to phenylephrine

- Uncontrolled hypertension (defined as blood pressure in adults > 150/95)

- Patients on anti-hypertensive medications are eligible if blood pressure is
controlled

- Enrollment in any other mucositis prevention study from screening up to day 45
post-stem cell transplant

- Patients who are not eligible to receive SCT with cyclophosphamide and total body
irradiation (TBI) conditioning because they do not meet transplant criteria are also
not eligible for this phenylephrine study

- General exclusion criteria for transplant include:

- Patients who have angina and/or congestive heart failure requiring treatment, or
who have had a myocardial infarction within the past year

- Patients who have had any complication that makes the risk of death during
transplantation from non-malignant causes greater than the risk of relapse

- Patients who have any active infection; if the infection is successfully treated,
the patient may be reconsidered for transplantation at a later date

- Patients with diabetes who are not controlled by medical management will be
ineligible

- Psychiatric illness requiring psychiatric counseling or medical intervention
other than antidepressant medications may make an individual ineligible and will
be considered on a case-by-case basis

- Psychosocial assessment by the bone marrow transplant team may identify
individuals for whom this form of therapy may be contraindicated; these decisions
will be based upon estimated adequacy of patient support systems and prediction
of patient's compliance with medications, required diagnostic procedures, and/or
follow-up care

- Patients who have an ECOG performance status of greater than 2

- Patients who have decreased pulmonary function due to any disorder as
demonstrated by a diffusion capacity of less than 50% of predicted, a FEV1 of
less than 60% of predicted, or a PO2 of less than 80mmHg on pulmonary function
testing

- Patients who have a resting ejection fraction of less than 50%

- Patients who have renal disease as demonstrated by a serum creatinine clearance
of greater than 2.0 mg/dL and/or a creatinine clearance of less than 50 mL/min

- Patients who are pregnant or breast feeding at the time of admission for
conditioning

- Any mental or physical condition, in the opinion of the principal investigator (PI) or
PI designee, which could interfere with the ability of the subject to understand or
adhere to the requirements of the study