Vaccine Therapy in Treating Patients With Newly Diagnosed Stage IV Kidney Cancer

OBJECTIVES:

Primary

- Determine the biological and clinical responses, in terms of measured T-cell responses,
of two different induction vaccination regimens comprising autologous dendritic cells
transfected with autologous tumor mRNA and human CD40 ligand in patients with newly
diagnosed stage IV clear cell renal cell carcinoma.

Secondary

- Determine safety of multiple administrations of this vaccine in these patients.

- Determine the overall feasibility of these regimens, in terms of ability to produce
vaccine within 13 weeks from the first leukapheresis.

- Determine the antitumor activity of this vaccine, in terms of objective response,
progression-free survival, and overall survival in these patients.

- Determine the applicability of several new assays characterizing the immunogenicity of
the vaccine as potency assays or surrogate parameters for biologic or clinical activity
in these patients.

- Correlate the delayed type hypersensitivity reactions with clinical activity of T-cell
immunity in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

All patients undergo nephrectomy or excisional biopsy or metastectomy to obtain and generate
autologous tumor mRNA. Approximately 4-8 weeks after surgery, patients undergo leukapheresis
to obtain peripheral blood mononuclear cells for the generation of dendritic cells (DC). The
DC are then transfected with autologous tumor mRNA and human CD40 ligand mRNA to produce a
vaccine. Patients are then assigned to 1 of 2 treatment groups.

- Group 1: Patients receive vaccine intradermally once every 14 days for a total of 5
injections followed by once every 28 days for 4 injections, and then once every 3
months in the absence of disease progression or unacceptable toxicity.

- Group 2: Patients receive vaccine intradermally once every 42 days for a total of 5
injections and then every 3 months in the absence of disease progression or
unacceptable toxicity.

Patients undergo blood collection periodically during study for biomarker correlative
studies.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: Approximately 26 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed clear cell renal cell carcinoma (RCC)

- Newly diagnosed disease

- Metastatic, stage IV disease (any T, any N, and M1)

- Confirmed diagnosis following nephrectomy on study OR has undergone nephrectomy for
RCC within the past 3 months AND meets the following criteria:

- Clear cell histology

- Metastatic lesion available for RNA isolation

- Stable disease not requiring any other antitumor treatment modality

- Prior nephrectomy following < stage IV disease with subsequent development of
metachronous metastasis allowed

- No requirement for bilateral nephrectomy for renal cancer

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- Bone metastases are not considered measurable disease

- No brain metastases by MRI

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Memorial Sloan Kettering Cancer Center risk group 0-1

- Body weight ≥ 30 kg

- Normal renal function in the contralateral kidney (kidney without tumor)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- WBC ≥ 4,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Absolute lymphocyte count ≥ 700/mm^3

- Hemoglobin ≥ 10 g/dL

- Transfusions for hemoglobin ≤ 10 g/dL allowed prior to or post-nephrectomy and
for up to 2 weeks prior to the first leukapheresis

- Creatinine < 1.5 mg/dL

- Total bilirubin < 2.0 mg/dL

- AST and ALT < 2 times upper limit of normal

- PT and PTT < 1.5 times control

- Corrected calcium < 10.5 mg/dL

- No cardiopulmonary disease

- No circulatory compromise

- No hepatic or renal dysfunction

- No uncontrolled hypertension

- No type I diabetes mellitus

- No active autoimmune disease including, but not limited to the following:

- Rheumatoid arthritis (RF-positive arthritis with current or recent flare)

- Inflammatory bowel disease

- Systemic lupus erythematosus (confirmed with anti-nuclear antibody ≥ 1:80)

- Ankylosing spondylitis

- Hashimoto's disease

- Scleroderma

- Multiple sclerosis

- Autoimmune hemolytic anemia

- Immune thrombocytopenic purpura

- No other malignancy within the past 5 years except adequately treated carcinoma in
situ of the cervix or nonmelanoma skin cancer

- No active infections

- HIV negative

- No viral hepatitis

- No history of hypercalcemia or symptomatic hypercalcemia requiring management

- No known hypersensitivity to dimethyl sulfoxide

- No other serious medical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 2 weeks since prior medications containing acetyl salicylic acid

- No prior therapy for renal cancer

- At least 2 months since prior and no concurrent chemotherapeutic agents

- At least 2 months since prior and no concurrent growth factors, cytokines, or white
lineage colony stimulating factors (e.g., filgrastim [G-CSF] and sargramostim
[GM-CSF])

- At least 2 months since prior and no concurrent immunosuppressive agents or
immunotherapy, including, but not limited to the following:

- Chronic topical corticosteroids (allowed to small areas of skin not near
injection sites with investigator approval)

- Inhaled corticosteroids (allowed for chronic obstructive pulmonary disease)

- Azathioprine

- Cyclosporine

- More than 28 days since participation in another investigational drug study

- Recovered from prior radiotherapy

- No planned or elective anticancer surgical treatment including target lesion
intervention

- Concurrent radiotherapy allowed for treatment of bone lesions

- Concurrent bisphosphonates allowed