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A Phase II Trial for Patients With Inflammatory (Stage IIIB) and Responsive Metastatic Stage IV Breast Cancer Using Busulfan, Melphalan and Thiotepa Followed by Autologous or Syngeneic PBSC Rescue and 12 Weeks of Post-Engraftment Immunotherapy With Low-Dose IL-2 and GM-CSF

Phase 2
19 Years
65 Years
Not Enrolling
Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, Inflammatory Breast Cancer, Male Breast Cancer, Progesterone Receptor-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage IIIB Breast Cancer, Stage IV Breast Cancer

Thank you

Trial Information

A Phase II Trial for Patients With Inflammatory (Stage IIIB) and Responsive Metastatic Stage IV Breast Cancer Using Busulfan, Melphalan and Thiotepa Followed by Autologous or Syngeneic PBSC Rescue and 12 Weeks of Post-Engraftment Immunotherapy With Low-Dose IL-2 and GM-CSF


I. To determine the event-free survival and survival of patients treated for inflammatory
(Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low
dose immunotherapy with IL2 and GM-CSF.


II. To determine the toxicity of a combination of low-dose IL-2 and GM-CSF in patients
following HDC with BUMELTT and PBSC support.


PREPARATIVE REGIMEN: Patients receive busulfan orally (PO) once every 6 hours on days -8,
-7, and -6; melphalan IV over 30 minutes on days -5 and -4; and thiotepa IV over 2 hours on
days -3 and -2.

TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell infusion on day 0.

POST-TRANSPLANT THERAPY: All patients receive tamoxifen citrate* PO once daily beginning
prior to aldesleukin (IL-2) and sargramostim (GM-CSF) therapy and continuing for 5 years or
until relapse (estrogen receptor [ER]- or progesterone receptor [PR]-positive patients) OR
until completion of IL-2/GM-CSF therapy (ER-negative or PR-negative patients). Eligible
patients receive IL-2 subcutaneously (SC) daily and GM-CSF SC 3 times weekly for 12 weeks
beginning 30-100 days after transplantation. Patients may receive radiotherapy after
completion of IL-2/GM-CSF treatment if no prior radiotherapy was given before

*Stage IV patients not receiving IL-2/GM-CSF therapy who received tamoxifen citrate as part
of adjuvant therapy and subsequently failed, receive oral anastrozole once daily for 5 years
or until progression instead of tamoxifen.

[*For postmenopausal patients, the choice and duration of hormonal therapy given in addition
to or an alternative to tamoxifen therapy will be at the physician's discretion]

Patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then
annually thereafter.

Inclusion Criteria:

- Patients with inflammatory (stage IIIb) or responsive stage IV breast cancer with
metastasis to soft tissue and/or bone; responsive stage IV disease is defined as
patients who achieve a PR (>= 50% reduction in measurable tumor burden) or CR
following initial chemotherapy for metastatic disease or patients with locally
recurrent disease (chest wall/axillary nodes) who are rendered disease-free following
surgery or radiation therapy without receiving chemotherapy; bone disease is
categorized as responsive if there is demonstrated sclerosis of prior lesions with no
new lesions

- Patients should have received 4-7 cycles of an Adriamycin and/or taxane-based regimen
for stage IIIb or stage IV disease; locally recurrent (chest wall/axillary nodes)
patients rendered NED by RT or surgery do not need to receive chemotherapy for stage
IV disease prior to Cytoxan/Taxol

- Patient has received Cytoxan 4 gm/m^2 x 1 and Taxol 250 mg/m^2 x 1 per FHCRC protocol
506.03; Cytoxan/Taxol must be given after all other chemotherapy is completed and
before transplant

- Stem cells were collected after mobilization with Cytoxan/Taxol or after mobilization
from an FHCRC approved cytokine protocol; if syngeneic collection, PBSC's were
collected by using G-CSF according to FHCRC protocol 753; patient has an adequate
number of peripheral blood stem cells stored (>= 2.5 x 10^6 CD34+ cells/kg)

- The patient must have the capacity to give informed consent; the patient must have
signed an approved consent form conforming with federal and institutional guidelines

- Hepatic function: Bilirubin =< 2 mg%; SGOT or SGPT =< 2.5 x institutional normal

- Renal function: Creatinine =< 2.0 mg/dl or a creatinine clearance >= 50 mg/min

- Pre-Study tests have been performed as outlined in the Study Calendar

- Patients will begin IL-2/GM-CSF therapy if they meet the following criteria

- Can start therapy 30 to 100 days after transplant

- Karnofsky performance status > 60

- ANC > 1,000 cells/mm^3 and platelets > 30,000/cells/mm^3 (transfusion independent)
for at least 5 days before starting therapy

- Total bilirubin =< 2.5 x upper limit of normal

- SGOT =< 2.5 x upper limit of normal

- Creatinine =< 2.0 mg/dl

Exclusion Criteria:

- Patients with a Karnofsky Performance Score less than 70

- Patients with a left ventricular ejection fraction less than 50 % (LVEF must be
performed in patients with symptoms of CHF, abnormal cardiac exam or history of
Adriamycin therapy total dose > 400 mg/m^2)

- Patient is pregnant

- Patient is seropositive for the human immunodeficiency virus

- Patients with a history of seizures

- Patients with hypersensitivity to E.coli preparations

- Patients with active auto-immune disease

- Patients with clinically significant pulmonary disease, i.e., diffusion capacity
corrected < 60% of predicted; patients with pulmonary problems should be evaluated
with appropriate pulmonary studies and/or consult

- Patients with a history of CNS lesion (brain or carcinoid meningitis)

- Patients with significant active infection precluding transplant

- Patients who have had more than one prior chemotherapy regimen for stage IV disease
or a prior transplant for any stage disease

- Patients who have had CD34+ selection of their PBSC products

- Patients will not receive IL-2/GM-CSF therapy if they:

- Are > 100 days from transplant

- Have documented disease progression after transplant

- Have an active infection

- Manifested cardiac complications during the initial transplant period, including
arrhythmias (that required therapy), congestive heart failure, angina, myocardial
infarct, or decreased LVEF to < 45%

- Currently have pericardial effusions, pleural effusions or ascites

- Manifested pulmonary toxicity during the initial transplant period and have a
diffusion capacity corrected =< 60%

- Are on steroids

- Currently have a Grade 3 toxicity from BuMelTT

- If the patient does not wish to receive the therapy

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Leona Holmberg

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Federal Government

Study ID:

PSOC 1605



Start Date:

November 1997

Completion Date:

Related Keywords:

  • Estrogen Receptor-negative Breast Cancer
  • Estrogen Receptor-positive Breast Cancer
  • Inflammatory Breast Cancer
  • Male Breast Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male
  • Inflammatory Breast Neoplasms



Fred Hutchinson Cancer Research Center/Puget Sound Oncology Consortium Seattle, Washington  98109