Allogeneic Breast Protocol 1: T-Cell Depleted Allogeneic Blood Stem Cell Transplantation Using an Immunoablative Conditioning Regimen in Metastatic Breast Cancer
18 Years
70 Years
Both
Breast Cancer
Trial Information
Allogeneic Breast Protocol 1: T-Cell Depleted Allogeneic Blood Stem Cell Transplantation Using an Immunoablative Conditioning Regimen in Metastatic Breast Cancer
OBJECTIVES:
- Determine the ability of T-cell-depleted allogeneic blood stem cell transplantation
after an immunoablative conditioning regimen to induce a state of mixed host/donor
chimerism in patients with metastatic breast cancer.
- Determine the ability of this treatment regimen to induce an allogeneic
graft-versus-tumor response in these patients.
- Determine the feasibility of giving other approved therapies to these patients at the
first sign of disease progression in order to stabilize or produce a minimal or partial
response.
OUTLINE: Patients receive chemotherapy comprising fludarabine IV over 30 minutes and
cyclophosphamide IV over 1 hour on days 1-4. Patients receive filgrastim (G-CSF) SC daily
beginning on day 5 and continuing until blood counts recover. Treatment repeats every 21
days for a maximum of 2 courses.
Patients receive a transplantation preparative regimen comprising fludarabine IV over 30
minutes and cyclophosphamide IV over 2 hours on days -6 to -3 (beginning on day 22 of
immune-depleting chemotherapy) followed by allogeneic peripheral blood stem cell
transplantation IV on day 0. Patients receive G-CSF SC daily beginning on day 0 and
continuing until blood counts recover, plus cyclosporine IV over 1-2 hours every 12 hours on
days -1 to 14 and then orally until day 40.
Patients with persistent malignant disease and less than grade II acute graft-versus-host
disease receive donor lymphocytes IV on days 42, 70, and 98.
Patients are followed twice weekly until day 100, and then at 6, 9, 12, 18, and 24 months.
PROJECTED ACCRUAL: A maximum of 70 patients will be accrued for this study within 24 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Stage IV breast cancer
- Measurable disease
- Progressive disease
- Increase in disease mass or less than partial response to therapy
- At least one prior chemotherapy regimen for metastatic disease and progressed
- Must have received prior therapy with a taxane and an anthracycline
- Estrogen/progesterone receptor-positive patients must have received and progressed on
at least one hormonal agent in adjuvant or metastatic setting
- Her2-neu-expressing patients must have received and progressed on trastuzumab
(Herceptin®) in adjuvant or metastatic setting
- Prior autologous stem cell transplantation allowed if less than complete response or
disease progression in adjuvant or metastatic setting
- Consenting first-degree relative with at least 5 out of 6 HLA-antigen match (may
include mismatch at the D locus)
- Hormone receptor status:
- Estrogen receptor status known
- Progesterone receptor status known
PATIENT CHARACTERISTICS:
Age:
- 18 to 70
Sex:
- Male or female
Menopausal status:
- Not specified
Performance status:
- Karnofsky 80-100%
Life expectancy:
- More than 6 months
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin ≤ 2 mg/dL
- SGOT < 4 times upper limit of normal
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
Renal:
- Creatinine ≤ 1.5 mg/dL
- Creatinine clearance ≥ 50 mL/min
Cardiovascular:
- Left ventricular ejection fraction > 45%
Pulmonary:
- DLCO ≥ 50% of predicted
Other:
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- Recovered from prior stem cell transplantation
Chemotherapy:
- See Disease Characteristics
Endocrine therapy:
- See Disease Characteristics
- No concurrent steroids
Radiotherapy:
- Not specified
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Michael R. Bishop, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
CDR0000067899
NCT ID:
NCT00020176
Start Date:
June 2000
Completion Date:
August 2007
Related Keywords:
- Breast Cancer
- stage IV breast cancer
- recurrent breast cancer
- male breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
| NCI - Center for Cancer Research | Bethesda, Maryland 20892 |
