Allogeneic Breast Protocol 1: T-Cell Depleted Allogeneic Blood Stem Cell Transplantation Using an Immunoablative Conditioning Regimen in Metastatic Breast Cancer


Phase 2
18 Years
70 Years
Not Enrolling
Both
Breast Cancer

Thank you

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