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

Primary Purpose

Breast Cancer

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

therapeutic allogeneic lymphocytes

cyclophosphamide

docetaxel

doxorubicin hydrochloride

fludarabine phosphate

peripheral blood stem cell transplantation

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage IV breast cancer, recurrent breast cancer

Eligibility Criteria

18 Years - 60 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00006261

First Posted

September 11, 2000

Last Updated

June 9, 2010

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00006261

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2010

Overall Recruitment Status

Withdrawn

Study Start Date

May 2000 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Donor lymphocytes may attack and destroy cancer cells. PURPOSE: This phase II trial is studying the effectiveness of combination chemotherapy, peripheral stem cell transplantation, and donor lymphocyte infusion in treating women with stage IV breast cancer.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

stage IV breast cancer, recurrent breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

therapeutic allogeneic lymphocytes

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Intervention Description

4-10 weeks after completion of salvage chemotherapy, patients achieving complete or partial remission or stable disease receive mini-conditioning comprised of cyclophosphamide IV over 2 hours on days -3 and -2.

Intervention Type

Drug

Intervention Name(s)

docetaxel

Intervention Description

Docetaxel IV over 1 hour. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

doxorubicin hydrochloride

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

fludarabine phosphate

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

peripheral blood stem cell transplantation

Intervention Description

Filgrastim (G-CSF) and sargramostim (GM-CSF) mobilized allogeneic peripheral blood stem cells (PBSC) IV on day 0.

Primary Outcome Measure Information:

Title

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.

Time Frame

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hillard M. Lazarus, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106-5065

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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