Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Women With Stage IV Breast Cancer
|ClinicalTrials.gov Identifier: NCT00020722|
Recruitment Status : Terminated (Lack of funding to continue study.)
First Posted : January 27, 2003
Results First Posted : March 30, 2015
Last Update Posted : February 17, 2016
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation plus biological therapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: This phase II trial is studying how well chemotherapy followed by peripheral stem cell transplantation plus biological therapy works in treating women with stage IV breast cancer.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Biological: therapeutic autologous lymphocytes Drug: Ifosfamide, carboplatin, and etoposide (ICE) regimen Drug: Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC) Procedure: Leukapheresis Procedure: peripheral blood stem cell transplantation (PBSCT)||Phase 2|
- Determine whether the use of autologous peripheral blood stem cell transplantation followed by immunotherapy with activated T cells in women with stage IV breast cancer improves progression-free survival (PFS) compared to a reported mean PFS in patients treated with second-line chemotherapy with matching inclusion criteria by published trials.
- Determine if this regimen improves clinical response and overall survival.
- Perform sequential immune monitoring studies, including phenotyping, cytotoxic assays, EliSpots for IFNγ, selected T-cell repertoire (Vβ analysis), HER2/new tetramer analysis, and serum tumor markers.
- Test correlations between immune function tests and clinical endpoints.
OUTLINE: Patients are stratified according to tumor classification (chemosensitive vs chemoresistant).
Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days followed by peripheral blood mononuclear cell (PBMC) collection for PBSCT and generation of activated T cells (ATC). The PBMC are treated ex vivo with monoclonal antibody OKT3 to form ATC. The ATC are expanded for 12-14 days in interleukin-2 (IL-2).
Patients then receive high-dose chemotherapy. Patients with chemosensitive disease receive cyclophosphamide IV over 1 hour, thiotepa IV over 1 hour, and carboplatin IV over 1 hour on days -4, -3, and -2. Patients with chemoresistant disease receive ifosfamide IV over 1 hour, etoposide IV twice daily, and carboplatin IV over 1 hour on days -8 to -3. Patients undergo autologous PBSC transplantation on day 0 or on both day 0 and day 1.
Patients then receive ATC IV over 15-20 minutes three times per week starting approximately on day +1 for three weeks and then once weekly for at least 6 doses.
After completion of study therapy, patients are followed periodically for up to 2 years after PBSC.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)|
|Study Start Date :||August 2007|
|Actual Primary Completion Date :||March 2013|
|Actual Study Completion Date :||March 2013|
|Experimental: therapeutic autologous lymphocytes||
Biological: therapeutic autologous lymphocytes
Drug: Ifosfamide, carboplatin, and etoposide (ICE) regimen
Immediately after pheresis, the lymphocytes will be activated with soluble monoclonal anti-CD3 antibody (OKT3) which cross-links the CD3 receptors on T cells and activates T cells.
The time for ATC infusions will vary from patient to patient, but the infusion rate will be based on the rate calculated from the endotoxin level in the cell product. All patients will be observed for at least 1 hr after an infusion.
Ifosfamide 2,500 mg/m2 given IV daily on day -8, -7, -6, -5, -4, and -3 prior to PBSCT. Ifosfamide 2,500 mg/m2 infused IV over 1 hour (hour 0-1) on days -8 to -3 for a total dose of 15,000 mg/m2.
Mesna will be administered per BMT Standard of Care Guideline at a dose of 25% of the total Ifosfamide dose 30 minutes prior to and then 3, 6, and 9 hours after ifosfamide daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 2500 mg/m2.
Carboplatin at a dose of 250 mg/m2 will be given daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 1500 mg/m2.
VP-16 (etoposide) at a dose of 200 mg/m2 will be given IV on days -8, -7, -6, -5, -4 and -3. The total dose of VP-16 given prior to PBSCT will be 2,400 mg/m2. VP-16 will be given 200 mg/m2
Other Names:Drug: Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC)
Cyclophosphamide will be given at a dose of 2000 mg/m2 in NS IV over one hour daily on days -4, -3, and -2 (total = 6000 mg/m2).
Thiotepa will be given at a dose of 167 mg/m2 in NS IV over one hour daily on days -4, -3, -2 (total = 500 mg/m2) as the preparative regimen followed by PBSCT on day 0.
Carboplatin will be given at a dose of 267 mg/m2 in D5W IV over one hour daily on days -4, -3, and -2.
Mesna will be administered per BMT Standard of Care Guidelines at a dose of 25% of the total cyclophosphamide dose 30 minutes prior to and then 3, 6, and 9 hours after cyclophosphamide daily on days -4, -3, and -2 prior to PBSCT for a total of 2000mg/m2.
Other Names:Procedure: Leukapheresis
Peripheral blood mononuclear cells (PBMC) will be collected by leukapheresis (for generation of ATC) prior to or post G-CSF (16 ug/kg/day) priming for collecting stem cells.Procedure: peripheral blood stem cell transplantation (PBSCT)
Will be collected either before or after peripheral blood stem cell collection for stem cell transplant.
- Disease-free Survival [ Time Frame: Length of time from day of transplant until recurrence or relapse. ]
- Overall Survival [ Time Frame: Length of time from day of transplant until death. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00020722
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201-1379|
|Study Chair:||Lawrence G. Lum, MD, DSc||Barbara Ann Karmanos Cancer Institute|