Allogeneic Transplantation Using Mini-Conditioning for Treatment of Stage IV Breast Cancer


Phase 2
18 Years
60 Years
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

Allogeneic Transplantation Using Mini-Conditioning for Treatment of Stage IV Breast Cancer


OBJECTIVES: I. Determine the tumor response in women with stage IV breast cancer who achieve
partial remission after a mini-conditioning regimen comprising fludarabine and
cyclophosphamide, followed by allogeneic peripheral blood stem cell transplantation (PBSCT),
and donor lymphocyte infusion (DLI). II. Determine the progression free survival in patients
who achieve complete remission after this treatment regimen. III. Determine whether DLI
exerts graft versus tumor effect in these patients. IV. Determine the acute and delayed
toxicities of this regimen in these patients. V. Determine the rates of durable hematologic
engraftment in patients treated with this regimen. VI. Determine the incidence and severity
of acute and chronic graft versus host disease in patients treated with this regimen. VII.
Determine the extent of chimerism in patients treated with this nonmyeloablative
conditioning regimen. VIII. Determine the rate and quality of immune reconstitution in
patients treated with this regimen. IX. Determine the event free and overall survival in
patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients receive salvage chemotherapy comprised of
docetaxel IV over 1 hour and doxorubicin IV over several minutes on day 1. Treatment
continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable
toxicity. Beginning within 4-10 weeks after completion of salvage chemotherapy, patients
achieving complete or partial remission or stable disease receive mini-conditioning
comprised of fludarabine IV over 30 minutes on days -8 to -4 and cyclophosphamide IV over 2
hours on days -3 and -2. Patients then receive filgrastim (G-CSF) and sargramostim (GM-CSF)
mobilized allogeneic peripheral blood stem cells (PBSC) IV on day 0. Beginning on day 120
after PBSC transplantation, eligible patients receive unmobilized donor lymphocyte infusion
(DLI) over 15-30 minutes. Treatment continues monthly for a total of 3 DLIs in the absence
of grade III or IV graft versus host disease or marrow aplasia. Patients are followed every
3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven stage IV epithelial breast cancer Must meet
one of the following conditions: Complete or partial remission or stable disease following
chemotherapy or radiotherapy Previously untreated disease No progressive disease after
prior therapy for metastatic breast cancer Overexpression of HER2 protein (2+ or 3+ by
immunohistochemistry) allowed if failed prior trastuzumab (Herceptin) therapy Measurable
disease by physical exam or external imaging studies OR Evaluable disease (e.g., abnormal
bone scan) Availability of a suitable HLA-A, B, and DR phenotypically identical sibling
donor No active CNS disease Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 to 60 Sex: Female Menopausal status: Not specified
Performance status: ECOG 0 or 1 Karnofsky 80-100% Life expectancy: At least 3 months
Hematopoietic: Absolute neutrophil count at least 1,000/mm3* Platelet count at least
100,000/mm3* * In patients receiving docetaxel Hepatic: SGOT and SGPT no greater than 5
times upper limit of normal (ULN)* Bilirubin no greater than ULN* Alkaline phosphatase no
greater than 2.5 times ULN Alkaline phosphatase no greater than 4 times ULN if SGOT and
SGPT no greater than ULN * In patients receiving docetaxel Renal: Creatinine no greater
than 2.0 mg/dL OR Creatinine clearance at least 50 mL/min Cardiovascular: Left ventricular
ejection fraction at least 40% by MUGA scan No cerebrovascular accident Pulmonary: DLCO,
FVC, and FEV1 at least 60% predicted Other: No active infection Not pregnant or nursing
Negative pregnancy test HIV negative No history of allergic reaction to taxane or
polysorbate 80 No grade 2 or worse peripheral neuropathy No second malignancy within the
past 2 years except basal cell skin cancer, carcinoma in situ of the cervix, or tumor
previously treated with curative intent No other clinically significant comorbid illnesses

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior
autologous stem cell transplantation Chemotherapy: See Disease Characteristics No prior
docetaxel At least 3 weeks since other prior chemotherapy Prior doxorubicin allowed if
cumulative dose less than 250 mg/m2 Prior paclitaxel allowed No more than 1 prior salvage
chemotherapy regimen for metastatic disease Endocrine therapy: Not specified Radiotherapy:
See Disease Characteristics Surgery: Not specified

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor response in women with stage IV breast cancer who achieve PR after a mini-conditioning regimen comprising fludarabine and cyclophosphamide, followed by PBSCT and DLI.

Outcome Time Frame:

Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Safety Issue:

No

Principal Investigator

Hillard M. Lazarus, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CWRU1199

NCT ID:

NCT00006261

Start Date:

May 2000

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms

Name

Location
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065