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

NCT00006261 | Withdrawn Phase 2 DMC

• 4 other identifiers: CWRU1199P30CA043703CWRU-1199NCI-G00-1855
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (1)

• 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.

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

Interventions

therapeutic allogeneic lymphocytes BIOLOGICAL

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.

cyclophosphamide DRUG

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.

docetaxel DRUG

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

doxorubicin hydrochloride DRUG

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.

fludarabine phosphate DRUG

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.

peripheral blood stem cell transplantation PROCEDURE

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

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

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Docetaxel; Doxorubicin; fludarabine phosphate; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Hillard M. Lazarus, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 11, 2000
• First Posted: April 29, 2004
• Study Start: May 1, 2000
• Last Updated: June 10, 2010

Record last verified: 2010-06

Locations

US (1)