Phase 1A/1B Study of PSA/IL-2/GM-CSF Vaccine for Recurrent Prostate Cancer in Hormone Naive and Hormone Independent Patients

In Phase 1A, hormone naive and hormone independent patients are enrolled in a 1:1 ratio. All
patients receive intradermal injections of the PSA/IL-2/GM-CSF induction vaccine at Weeks 1,
2, 3, 7, 11 and 15.

In Phase 1B, which will be initiated after Phase 1A, will first receive the induction vaccine
(PSA/IL-2/GM-CSF) according to the same schedule as patients in Phase 1A. Then, in eligible
Phase 1B patients, following the induction vaccine regimen, alternating maintenance
vaccination will be administered as follows: at Weeks 23, 31, and 39, IL-2 alone will be
administered; at Weeks 27, 35, and 43, the complete vaccine (PSA/IL-2/GM-CSF) will be
administered.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate

- Age greater than18 years

- Rising serum PSA levels documented by 3 values over the last 6 months prior to study
enrollment. Each value must be greater than 2 weeks from the previous value.

- Patients with rising PSA must have had either 1) prior definitive therapy including
surgery or radiation therapy (hormone-naïve, defined as hormone-naïve patients and
patients who received hormone therapy in the past who currently have total
testosterone greater than 50 ng/dL), or 2) hormone suppressive therapy as documented
by surgical castration or a serum testosterone value less than 50 ng/dL
(hormone-independent). Patients must have completed these therapies for at least 6
months but no longer than 20 years prior to enrollment

- PSA value within 4 weeks of starting therapy less than 20 ng/mL for hormone-naïve
patients (defined as hormone-naïve patients and patients who received hormone therapy
in the past who currently have total testosterone greater than 50 ng/dL) or less than
60 ng/mL for hormone-independent patients.

- Patients must have the following laboratory values: ANC greater than 1500/mcL,
platelet count greater than 100,000/mcL, hemoglobin greater than 10 g/dL, bilirubin
less than 1.5 x upper limits of normal, AST less than 1.5 x upper limits of normal

- Patients must have adequate lung function, as defined by oxygen saturation greater
than or equal to 90% by pulse oximetry

- Patients must have QTc interval less than 450 msec

- Patients must have adequate EGFR greater than 30 mL/min per 1.73 m2 (per VA formula
and adjusted for gender and race)

- Patients with female partners of childbearing potential must use at least one form of
Investigator-approved contraception while on-study and for 30 days after their last
administration of study investigational therapy. Acceptable birth control options
include: a) surgical sterilization (subject and/or subject's partner), b) approved
hormonal contraceptives or therapies (such as birth control pills, Depo-Provera, or
Lupron Depot), c) barrier methods (such as a condom or diaphragm) used with a
spermicide, and d) an intrauterine device (IUD).

Exclusion Criteria:

- Presence of documented neuroendocrine differentiation on the original pathology report

- Evidence of metastatic disease

- Immune compromised patients including but not limited to: systemic immune suppressive
medications within 6 weeks of enrolling; HIV-positive and below normal CD4 lymphocytes
(less than 500 cells per microliter). Patients must be tested for HIV seropositivity
and CD4 lymphocyte count to be eligible for the study

- Prior malignancy. Patients with nonmelanoma skin cancer or other cancers with greater
than 3 years without evidence of disease recurrence are eligible

- Inability to give informed consent

- Any condition that, according to the investigator, would make the patient an
inappropriate study candidate.

- Patients with pulmonary disease limiting daily function or requiring oxygen
supplementation

- Patients with significant cardiac disease including heart failure that meets New York
Heart Association (NYHA) class III and IV definitions, history of myocardial
infarction within six months of study entry, uncontrolled dysrhythmias, or QTc greater
than or equal to 450 msec

- Patients with existing autoimmune disorders (IL-2 and GM-CSF carry a theoretical
clinical risk of exacerbating underlying autoimmune disorders)