UARK 2014-21 A Phase II Trial of Oncolytic Virotherapy by Systemic Administration of Edmonston Strain of Measles Virus

The drug used in this trial is a modified version of the measles virus used to vaccinate
children. The virus has been altered by having an extra gene (piece of DNA) added to it to
allow a protein called NIS to be inserted into it. NIS is normally found in the thyroid gland
( a small gland in the neck) and helps the body concentrate iodine. Having this additional
gene will make it possible to track where the virus goes in the body.

Inclusion Criteria:

- Relapsed patients must have a confirmed MM diagnosis with high-risk disease as defined
by GEP70 risk score ≥ 0.66 or GEP80 gene score of ≥ 2.48 or metaphase cytogenetic
abnormalities or LDH ≥ 360 U/L due to MM (Rule out hemolysis, infection and contact PI
for clarification if any doubt). Patients must have relapsed after auto-PBSCT followed
by further chemotherapy

- ≥2 months must have elapsed after the last peripheral blood stem cell transplant prior
to enrollment

- Zubrod ≤ 2, unless solely due to symptoms of MM-related (bone) disease

- Patients must have a platelet count of ≥ 20,000/µL within 45 days of registration,
unless lower levels are explained by extensive BM plasmacytosis or extensive prior
therapy

- Patients must be at least 18 years of age and not older than 75 years of age at the
time of registration

- Participants must have preserved renal function as defined by a serum creatinine level
of ≤ 3 mg/dL within 45 days of registration

- Participants must have an ejection fraction by ECHO or MUGA scan ≥ 40% within 45 days
prior to registration

- Patients must have adequate pulmonary function studies > 50% of predicted on
mechanical aspects (FEV1, etc) and diffusion capacity (DLCO) > 50% of predicted within
45 days prior to registration. If the patient is unable to complete pulmonary function
tests due to MM related pain or condition, exception may be granted

- Patients must have signed an IRB-approved informed consent and Health Insurance
Portability and Accountability Act (HIPAA) authorization form

- Patients must have anti-MV IgG titer of ≤ 0.5U/mL (Mayo clinic assay). Mayo Clinic
will also assay the patients' IgM titer and perform a neutralizing antibody
plaque-assay to determine recent MV exposure and the ability of the patients'
circulating antibodies to inhibit MV propagation on Vero cells, respectively. While
these tests are additional indicators of patient eligibility, final enrollment
decision will be determined by IgG levels

Exclusion Criteria:

- Patients may not be positive for the Human Immunodeficiency Virus (HIV)

- History of poorly controlled hypertension, diabetes mellitus, or any other serious
medical illness or psychiatric illness that could potentially interfere with the
completion of treatment according to this protocol or could be considered to be an
exclusion criterion deemed by the PI

- Patients must not have prior malignancy, except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
patient has not received treatment for one year prior to enrollment. Other cancers
will only be acceptable if the patient's life expectancy exceeds three years as
determined by the PI

- Pregnant or nursing women may not participate. Women of childbearing potential must
have a negative pregnancy test documented within one week of registration. Women/men
of reproductive potential may not participate unless they have agreed to use an
effective contraceptive method

- Exposure to household contacts ≤ 15 months old or household contact with known
immunodeficiency