A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for Treatment of Stage IV Melanoma

A-dmDT390-bisFv(UCHT1) (Resimmune™), an anti-T cell immunotoxin is currently being studied
as a treatment for cutaneous T cell lymphoma and other CD3+ malignant diseases (FDA IND
Number: 100712, Scott and White Protocol 071163). During the course of this study, data
accumulated that Resimmune could be acting as an immunomodulator. This was based on the
observation that four out of six partial responses converted to complete responses at times
ranging between 6 and 24 months following the completion of the 4-day treatment protocol and
no other treatment took place.

The purpose of this trial is to test the hypothesis that Resimmune can act as an
immunomodulator of late stage metastatic melanoma when combined with palliative radiation to
induce the priming of activated T cells with tumor antigens. The primary objective of this
study is to determine the safety of combining Resimmune with palliative radiation therapy in
patients with stage IV melanoma. A secondary objective is to document the tumor response and
duration of response at irradiated and unirradiated sites (the abscopal effect). An
additional secondary objective is to determine if T cell activation occurs following
administration of A-dmDT390-bisFv(UCHT1) and local radiation to a metastatic lesion of
melanoma.

Inclusion Criteria:

- All patients must have histologically proven stage IV metastatic melanoma consisting
of at least two lesions

- Patients must have a performance status of < 2 on Eastern Cooperative Oncology Group
scale (see Appendix).

- Patients must have bilirubin < 1.5 mg/dL, transaminases < 2.5 X ULN, albumin > 3
gm/dL, creatinine < 2.0 mg/dL, adequate pulmonary function by physical exam and pulse
oximetry and adequate cardiac reserve (EF > 50% normal). Patients must have a normal
echocardiogram without any evidence of cardiac chamber hypertrophy, dilatation or
hypokinesis.

- Patients must give written informed consent prior to registration.

- Females and males must be willing to use an approved form of birth control while on
this study and for 2 weeks after completion.

- Patients of ages 18-80 are eligible provided they have stage IV melanoma and are
negative for BRAF or have failed BRAF inhibitor treatment or if they have failed or
are intolerant to other established therapy known to provide clinical benefit for
their condition or if they have been adequately consented and agreed to forgo FDA
approved clinically meaningful therapy

Exclusion Criteria:

- Inability to give informed consent because of psychiatric problems, or complicated
medical problems.

- Serious concurrent medical problems, uncontrolled infections, or disseminated
intravascular coagulopathy (DIC).

- Preexisting cardiovascular disease, the only exception being well controlled
essential hypertension with a sitting blood pressure of <155 systolic and <90
diastolic without any evidence of structural heart disease or one episode of
myocardial infarction > 8 months ago. A past history of the any of the following are
exclusions: congestive heart failure, atrial fibrillation, pulmonary hypertension,
anticoagulant drug therapy, thromboembolic events, cardiomyopathy or a myocardial
infarction within the past 8 months.

- Pregnant or nursing women will be excluded from study.

- History of congestive heart failure.

- History of cirrhosis of the liver