Phase II Study of Allo LMI Vaccine With IL-2 for Stable Metastatic Breast Ca

OBJECTIVES:

Primary

- To determine the efficacy of allogeneic large multivalent immunogen (LMI) vaccine and
aldesleukin, as defined by clinical benefit rate (percentage of patients demonstrating a
complete response, partial response, or disease stabilization as assessed by RECIST
criteria), in women with stable metastatic breast cancer.

Secondary

- To measure the immune response in patients treated with this regimen.

- To determine the progression-free survival of patients treated with this regimen.

- To determine the 1- and 2-year overall survival rates in patients treated with this
regimen.

- To determine the safety profile and toxicity of this regimen in these patients.

OUTLINE: Patients receive allogeneic large multivalent immunogen (LMI) vaccine intradermally
on day 1 and aldesleukin subcutaneously on days 7 and 8. Treatment repeats every 28 days in
the absence of disease progression or unacceptable toxicity. Patients with disease
progression after 2 courses of vaccine therapy resume the chemotherapy regimen for which
prior disease stabilization was achieved. Beginning 2-4 days after completion of
chemotherapy, patients receive one dose of LMI vaccine followed by aldesleukin on days 7 and
8. Patients achieving at least stable disease continue to receive LMI vaccine and aldesleukin
as above. Treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.

Peripheral blood mononuclear cell samples are collected periodically for research studies.
Samples are analyzed to assess the frequency of leukocyte subsets (including B cells, T
cells, NK cells, and monocytes) via flow cytometry; frequency of T-regs (T cells that express
CD4, CD25, and FoxP3); and responses to keyhole limpet hemocyanin and tetanus toxoid via
ELISA assay. Other immunological studies are also performed.

After completion of study therapy, patients are followed every 3 months.

Inclusion criteria:

- Stage IV, metastatic breast cancer, confirmed by histology or cytology.

- Disease must be refractory to hormone therapy for tumors that estrogen and/or
progesterone receptor positive

- Disease must be refractory to trastuzumab for tumors that are HER2 positive

- Disease must be responsive to chemotherapy such that regression or at least
stabilization occurs

- Stable disease is defined as neither sufficient shrinkage to qualify for
partial response nor sufficient increase to qualify for progressive disease

- Measurement of regressed or stable disease must be confirmed by repeat
evaluation no less than 4 weeks after the initial determination.

- Prior systemic chemotherapy, immunotherapy, biological therapy, or investigational
drug 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.

- There is no limit as to the number of previous chemotherapy regimens received.

- Disease status may be measurable or non-measurable

- Karnofsky performance status >70%

- Women, age 18 years or older

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

- Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count
(ANC) ≥ 1.5 x 10^9/L, platelets ≥75 x 10^9/L, and hemoglobin ≥ 8.0 g/dL

- Hepatic: bilirubin ≤ 3 times the upper limit of normal (× ULN) for patients
without tumor involvement of the liver and ≤ 5 X ULN for patients with tumor
involvement of the liver; aspartate transaminase (AST) ≤ 2.5 × ULN for patients
without tumor involvement of the liver and ≤ 5 X ULN for patients with tumor
involvement of the liver

- Renal: creatinine ≤ 2.0 mg/dL

- Must share at least one class I HLA allele with the HLA-type SKBR3 cell (class I
alleles A2, A3, B14, B40, C3, C8)

- 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). Patients who have had tetanus toxoid
within the last 7 years will not receive the tetanus vaccine component. For patients
who do not know the year of their last tetanus vaccine, tetanus toxoid will be given
per protocol. Subjects allergic to seafood will not be co-enrolled into MT1996-06.

- Women of childbearing potential and their partners are required to use an effective
method of contraception (ie, a hormonal contraceptive, intra-uterine 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 untreated or active brain metastases or positive brain scan at enrollment.
Patients with previously treated brain metastases are eligible if stable by CT or MRI
for at least 3 months.

- Concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the
cervix

- Active infection

- Solid organ transplantation or autoimmune diseases requiring systemic
immunosuppressive therapy; however, topical or inhalational steroids are allowed.

- Symptomatic pulmonary disease (symptoms of dyspnea or rales, wheezes or rhonchi on
physical exam) will require pulmonary function testing (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.

- 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).

- 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.