Pilot Study of Autologous T Cells and/or IL-2 for the Enhancement of Immune Reconstitution After Dose-Intensive Chemotherapy for Breast Cancer

Inclusion Criteria

PRE-CHEMOTHERAPY ELIGIBILITY:

Patients must have a histologically confirmed diagnosis of stage II, III, or IV
infiltrating breast cancer; stage II patients must be considered high risk with greater
than four positive axillary lymph nodes at primary surgery. Patients with metastatic
disease must have their relapse confirmed pathologically. All pathological material must
be reviewed and the diagnosis confirmed by the Department of Pathology at the NIH Clinical
Center prior to acceptance on the protocol.

Patients enrolled on this protocol may receive chemotherapy by one of the following
mechanisms: (1) Any dose intensive chemotherapy regimen given as part of a separate NCI
breast cancer protocol. In such a case, prior approval of the principal investigator for
that study should be obtained. It must be emphasized that no clinical or research
endpoints of the chemotherapy protocol must be compromised by participation in this immune
reconstitution protocol.

(2) In some cases, patients may receive non-experimental chemotherapy from their referring
physicians. Patients may not be enrolled on this study if they are to receive
chemotherapy as part of an experimental study performed outside of the NCI; patients who
are receiving high-dose chemotherapy requiring stem cell support at other institutions are
specifically excluded from participation in this study. The determination of whether
non-experimental chemotherapy qualifies as dose intensive will be made by the principal
investigator.

All stage II and III patients must represent a new diagnosis and must have received no
prior chemotherapy.

Patients with metastatic disease can represent a new diagnosis as stage IV, or may have
metastatic disease that represents a relapse after adjuvant therapy for any other stage of
breast cancer. However, a prior of one year must have elapsed since the completion of
adjuvant chemotherapy.

Patient must have a Hct of greater than or equal to 24%, a WBC count of greater than or
equal to 3000 per mm(3), and platelets greater than or equal to 100,000 per mm(3) at the
time of enrollment.

Patients must have no history of abnormal bleeding tendency or predisposition to
infection.

Serum creatinine of less than 1.5 or Crcl of less than 60 cc per min. Higher values may
be allowed if it is determined by the principal investigator that elevated values are due
to tumor impairment of organ function.

AST and ALT less than 3 times the upper limits of normal. Higher values may be allowed if
it is determined by the principal investigator that elevated values are due to tumor
impairment of organ function.

In the presence of known pulmonary disease of symptoms, patients must have a pO2 greater
than 65 and FEV1 and FVC greater than 65% of predicted (unless directly due to tumor
involvement prior to therapy).

LVEF greater than or equal to 45% post-chemotherapy, as measured by MUGA or 2-D
echocardiogram.

All patients must be free of a significant history or active symptomatology of coronary
artery disease, congestive heart failure, neurologic disease, or chronic obstructive
pulmonary disease.

Patients must have a Karnofsky performance score of greater than 70% (ECOG 0 or 1) and a
life expectancy of at least three months.

Patients must be able to give informed consent.

POST-CHEMOTHERAPY ELIGIBILITY:

After completion of dose intensive chemotherapy, patients must continue to meet the
eligibility criteria above. However, for patients who are to receive only autologous T
cells (and no IL-2 therapy), cardiac ejection fraction will not represent a treatment
eligibility criteria. In addition, patients must meet the criteria as outlined below.

To proceed with the protocol after completion of dose intensive chemotherapy, stage II and
III patients must have no evidence of disease. Patients requiring adjuvant radiation
therapy will receive this prior to proceeding with this protocol. Patients with
metastatic disease must have demonstrated a least a partial response to chemotherapy
(greater than 50% reduction in measurable disease).

To be eligible to proceed with T cell infusion and/or IL-2 administration after completion
of chemotherapy, patients must have a Hb of greater than or equal to 9, an ANC greater
than or equal to 1000, and a platelet count of greater than or equal to 75,000.

Patients must have recovered from any non-hematologic toxicities of dose-intensive
chemotherapy and radiation therapy prior to receiving T cell infusions or IL-2.

All women will be tested for pregnancy at enrollment and prior to T cell transfer or IL-2
treatment; individuals must not be pregnant.

Patients must not be HIV positive or have Hepatitis B or C infection.

Patients must not have a chronic need to steroid or anti-coagulant therapy. However, for
patients who are to receive only autologous T cells, steroid or anti-coagulant therapy
will not be an exclusion criteria.

Patients must not present with any unusual medical or psychiatric risk.