Allogeneic Peripheral Stem Cell Transplantation in Treating Patients With Stage IV Breast Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00020176

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of allogeneic peripheral stem cell transplantation in treating patients who have stage IV breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: filgrastim Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2000

Actual Study Completion Date :

Aug 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
2	NCI - Center for Cancer Research	Bethesda	Maryland	United States	20892