Aldesleukin With or Without Vaccine Therapy in Treating Patients With Stage IV Melanoma

OBJECTIVES:

Primary

- To compare the progression-free survival of patients with stage IV melanoma treated with
aldesleukin with vs without allogeneic large multivalent immunogen melanoma vaccine
LP2307.

Secondary

- To compare the clinical response in patients treated with these regimens.

- To compare the 1- and 2-year survival rates in patients treated with these regimens.

- To determine whether an immune response is generated after vaccination in these
patients.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive allogeneic large multivalent immunogen melanoma vaccine LP2307
intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment
repeats every 28 days for 12 courses in the absence of disease progression or
unacceptable toxicity.

- Arm II (control): Patients receive aldesleukin SC on days 1 and 2. Treatment repeats
every 28 days for 12 courses in the absence of disease progression or unacceptable
toxicity. Patients with disease progression may cross over and receive treatment on arm
I.

Patients undergo blood sample collection periodically for correlative laboratory studies.
Samples are analyzed for immune responses to keyhole limpet hemocyanin and tetanus toxoid
(control antigens) by ELISA assay; IFN-γ production by CD8 T cells in response to
melanoma-derived peptides by ELISpot assay; delayed-type hypersensitivity response to
vaccination; and frequency of peripheral blood lymphocytes, including T cells, B cells, NK
cells, and monocytes, by flow cytometry.

- Arm III Crossover: Patients who have progressive disease on Arm II will be offered
crossover to Arm I provided they continue to meet all study criteria.

After completion of study treatment, patients are followed every 2 months for 1 year, every 3
months until disease progression, and then periodically thereafter.

Inclusion Criteria:

- Stage IV melanoma.

- Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed if at
least 4 weeks since last treatment. Patient must recover from the acute toxic effects
of the treatment prior to study enrollment.

- Disease status must be that of measurable or nonmeasurable disease as defined by Solid
Tumor Response Criteria (RECIST)

- Karnofsky performance status >70% (Eastern Cooperative Oncology Group 0-1)

- Age 18 years or older

- Adequate organ function within 14 days of study enrollment including the following:

- Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count
(ANC) ≥ 1.5 x 10^9/L, platelets ≥100 x 10^9/L, and hemoglobin ≥ 10 g/dL

- Hepatic: bilirubin < 3 times the upper limit of normal (× ULN), aspartate
transaminase (AST) < 3 × ULN

- Renal: creatinine ≤ 2.0

- Must share at least one class I HLA allele with the HLA-type SK23-CD80+ cell (class I
alleles (A1, A2, B7, B8, C7))

- Meets eligibility criteria for and agrees to enroll in "MT1999- 06: Vaccination with
Tetanus Toxoid and Keyhole Limpet Hemocyanin (KLH) to Assess Antigen-Specific Immune
Responses" (IRB # 9904M01581, CPRC #2002LS032)

- Women of childbearing potential and men whose partners are of childbearing potential
are required to use an effective method of contraception (ie, a hormonal
contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide,
or abstinence) during the study and for 3 months after the last dose of study drug.

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

Exclusion criteria:

- History of brain metastases or positive brain scan at on-study

- Immunosuppressive therapy i.e., prednisone or organ transplant patients, however
topical or inhalational steroids are allowed.

- Autoimmune diseases requiring immunosuppressive therapy.

- History of symptomatic pulmonary disease will have pulmonary function tests (PFTs)
performed. Patients with symptoms of dyspnea or rales, wheezes or rhonchi on physical
exam will undergo PFTs. Those with FEV1 <50% of predicted or corrected DLCO <50% are
not eligible.

- Patients with cardiac disease such as recent myocardial infarction (< 3 months prior),
unstable angina, or heart failure requiring medical intervention will undergo cardiac
evaluation. Cardiac testing may include ECG, MUGA or echocardiogram, and/or thallium
stress test as indicated to evaluate cardiac risks. Those patients with
exercise-induced ischemia or an ejection fraction by MUGA or echocardiogram < 40% are
not eligible.

- Due to the origin of the KLH protein, patients with a history of seafood allergy are
excluded from receiving KLH.

- Hypersensitivity to any component of the vaccine, including Thimerosal, a mercury
derivative, is a contraindication (taken from tetanus toxoid package insert).

- The occurrence of any type of neurologic symptoms to tetanus vaccine in the past is a
contraindication to further use (taken from tetanus toxoid package insert).

- Subjects who have had tetanus toxoid within the last 7 years will not receive the
tetanus vaccine component of this

- Pregnant (positive pregnancy test) or lactating women. Use of LMI vaccine during
pregnancy is not approved for use by the FDA during pregnancy. IL-2 is pregnancy
category C - risk in pregnancy cannot be ruled out.