Trial Information

A PILOT TRIAL OF INTERLEUKIN-2 WITH G-CSF AS PRIMING THERAPY FOR PERIPHERAL BLOOD STEM CELL HARVESTING IN PATIENTS WITH ADVANCED BREAST CANCER: STAMP V HIGH DOSE CHEMOTHERAPY, STEM CELL INFUSION AND POST-INFUSION G-CSF AND INTERLEUKIN-2

OBJECTIVES: I. Estimate the maximum tolerated dose of continuous infusion interleukin-2
(IL-2) that can be combined with a standard dose of filgrastim (G-CSF) to stimulate
peripheral blood stem cells (PBSC) for harvest in patients with advanced breast cancer. II.
Assess PBSC engraftment following high dose cyclophosphamide, thiotepa, and carboplatin (the
STAMP V regimen) supported by G-CSF or IL-2/G-CSF hematopoietic support in patients who
underwent the same pretransplant PBSC stimulation. III. Characterize the toxic effects of
combined IL-2 and G-CSF. IV. Compare immune function changes following IL-2/G-CSF and G-CSF
alone by assessing expression of CD56/CD56-bright, CD3, and CD25; natural killer cell and
lymphokine activated killer cell activity; T-cell responses (TT, HER2/neu); and serum levels
of interleukin-6, tumor necrosis factor, and G-CSF. V. Compare the effects on the expression
of circulating hematopoietic progenitor cells (CD34+, CFU-GM, and BFU-GM) of a range of IL-2
doses when combined with G-CSF to those achieved with G-CSF alone. VI. Compare the time to
neutrophil and platelet recovery, requirements for red blood cell and platelet transfusion,
and time to hospital discharge in patients receiving IL-2/G-CSF-primed vs. G-CSF-primed PBSC
following STAMP V chemotherapy. VII. Compare the feasibility, toxicity, and hematologic and
immunologic effects of post-PBSC infusion of IL-2/G-CSF vs. G-CSF alone. VIII. Assess the
response rate, duration of response, and disease free interval of patients with advanced
breast cancer treated with STAMP V with PBSC rescue. IX. Assess the presence of cytokeratin
as a marker of minimum residual disease when measured in blood and marrow by polymerase
chain reaction during and following treatment.

OUTLINE: Patients are assigned to 1 of 4 treatment groups for peripheral blood stem cell
stimulation (priming) and for therapy after stem cell transplantation. All patients receive
priming therapy with filgrastim (G-CSF) alone or with interleukin-2 (IL-2), then have stem
cells harvested. Patients with adequate harvest receive high dose cyclophosphamide,
thiotepa, and carboplatin (STAMP V) followed by stem cell rescue with subsequent G-CSF with
or without IL-2, as follows: Arm I receives G-CSF alone for priming and following stem cell
transplant. Arm II receives G-CSF priming alone and G-CSF/IL-2 following transplant. Arm III
receives various doses of G-CSF/IL-2 priming and G-CSF following transplant. Arm IV receives
various levels of G-CSF/IL-2 priming and fixed doses of G-CSF/IL-2 following transplant.
Cohorts of 3-6 patients each are treated on each treatment arm and at escalating doses of
IL-2. The maximum tolerated dose is defined as the dose at which less than 2 of 6 patients
experience dose limiting toxicity. Patients are followed for disease progression and
survival.

PROJECTED ACCRUAL: Approximately 36 patients will be accrued for this study over 18-24
months; a maximum of 12 patients will receive G-CSF priming alone (6 without and 6 with
post-PBSC IL-2).