Breast Cancer
Conditions
Keywords
stage IV breast cancer, male breast cancer, recurrent breast cancer
Brief summary
RATIONALE: Giving chemotherapy before a donor natural killer (NK) cell infusion helps stop the growth of tumor cells. It also helps stop the patient's immune system from rejecting the donor's cells. Giving NK cells from a related donor may kill the tumor cells. PURPOSE: This study furthers the research of previous studies (MT2003-01 and MT2004-25) which were to determine a specific preparatory regimen (cyclophosphamide and fludarabine) could create an environment in which infused NK cells can grow and effectively treat patients with relapsed AML. This study will test the previous regimen in patients with breast cancer.
Detailed description
We believe that administration of related allogeneic (donor) natural killer cells along with IL-2, rather than autologous natural killer cells will provide the most effective anticancer therapy in this setting, and wish to test this approach. To do this, we will select a related donor who is partially HLA-matched with the study subject, to increase the likelihood that donor natural killer cells will kill the subject's cancer cells. We will also give chemotherapy drugs to increase the subject's tolerance for the donor natural killer cells. We will test the use of donor natural killer (NK) cell infusions. The immune system has a special way that it sees and identifies cancer cells or foreign agents (like viruses). The subject's own NK cells may not attack their cancer because NK cells see the tumor cells as self (a coating on the cell surface identifies a cell as self or non-self). We have reason to believe that NK cells may not kill cancer cells because NK cells have special receptors that turn them off when they encounter cancer cells (by seeing them as self). We may be able to get around this problem by using donor NK cells. Finally, subjects will receive a dose of subcutaneous IL-2 3 times a week (for 2 weeks) which has been proven safe in our previous studies to stimulate the natural killer cells.
Interventions
DRUGFludarabine
administered intravenously 25 mg/m\^2 times 5 doses
DRUGCyclophosphamide
administered intravenously 60 mg/kg days times 2 doses.
RADIATIONTotal body irradiation
200 cGy (gray) on day -1
Infused cell dose is within the range of 1.5-8.0 x 10\^7/kg. Cell counts are based on total cells infused after the activation culture and washing determined on the morning of infusion.
BIOLOGICALInterleukin-2
administered subcutaneously (10 MU) 3 times per week for 6 doses
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of metastatic breast cancer that has progressed on or failed at least one salvage chemotherapy regimen for metastatic disease and that meets the following disease specific related criteria: * Measureable metastatic disease per Response Evaluation Criteria In Solid Tumor (RECIST) - bone only not eligible. * Disease progression while receiving prior therapy with a hormonal agent (if estrogen/progesterone receptor-positive) and/or trastuzumab (Herceptin®) (if HER2-neu positive) * Brain metastases allowed provided they are stable for ≥ 3 months after prior treatment * Related HLA-haploidentical natural killer cell donor available (by ≥ class I serologic typing) * Male or female * Performance status 50-100% * Platelet count ≥ 80,000/mm³ (unsupported by transfusions) * Hemoglobin ≥ 9 g/dL (unsupported by transfusions) * Absolute neutrophil count ≥ 1,000/mm³ (unsupported by sargramostim \[GM-CSF\] or filgrastim \[G-CSF\]) * Creatinine ≤ 2.0 mg/dL * Liver function tests \< 5 times normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * LVEF \> 40%\* * Pulmonary function \> 50%\* (DLCO corrected AND FEV\_1) * No active infection (i.e., afebrile, off antibiotics, and no uninvestigated radiologic lesions)
Exclusion criteria
* At least 3 days since prior prednisone or other immunosuppressive medications * No other concurrent therapy for cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Had Expansion of Natural Killer Cells | Day 14 | Successful Natural Killer (NK) cell expansion is defined as detection of an absolute circulating donor-derived NK cell count of \>100 cells/ul of whole blood 14 days after infusion with \<5% donor T and B cells in mononuclear population (in metastatic breast cancer patients). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients by Disease Response | 6 Months, 1 Year | Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria: * Complete Response (CR: Disappearance of all target lesions * Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD * Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions of appearance of one or more new lesions of clinical benefit (CB; stable disease for greater than 6 months. |
| Number of Patients Who Died While on Study | Within 100 days, After 100 days | Number of patients who died within 100 days and after 100 days of natural killer (NK) treatment with or without total body irradiation. |
| Overall Median Number of Days Patients Alive After Treatment | First Day of Treatment Until Death | Calculated median number of days of survival (patients alive days after treatment). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NK Cells With or Without Total Body Irradiation Patients receiving natural killer cell infusion, fludarabine and cyclosphosphamide preparatory regimen, and with or without total body irradiation for treatment of metastatic breast cancer. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | NK Cells With or Without Total Body Irradiation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 41.1 years STANDARD_DEVIATION 7.7 |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 6 / 6 |
Outcome results
Primary
Number of Patients Who Had Expansion of Natural Killer Cells
Successful Natural Killer (NK) cell expansion is defined as detection of an absolute circulating donor-derived NK cell count of \>100 cells/ul of whole blood 14 days after infusion with \<5% donor T and B cells in mononuclear population (in metastatic breast cancer patients).
Time frame: Day 14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NK Cells With or Without Total Body Irradiation | Number of Patients Who Had Expansion of Natural Killer Cells | 0 Participants |
Secondary
Number of Patients by Disease Response
Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria: * Complete Response (CR: Disappearance of all target lesions * Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD * Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions of appearance of one or more new lesions of clinical benefit (CB; stable disease for greater than 6 months.
Time frame: 6 Months, 1 Year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NK Cells With or Without Total Body Irradiation | Number of Patients by Disease Response | Stable Disease | 4 Participants |
| NK Cells With or Without Total Body Irradiation | Number of Patients by Disease Response | Progressive Disease | 2 Participants |
Secondary
Number of Patients Who Died While on Study
Number of patients who died within 100 days and after 100 days of natural killer (NK) treatment with or without total body irradiation.
Time frame: Within 100 days, After 100 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NK Cells With or Without Total Body Irradiation | Number of Patients Who Died While on Study | Died within 100 days | 1 Participants |
| NK Cells With or Without Total Body Irradiation | Number of Patients Who Died While on Study | Died after 100 days | 5 Participants |
Secondary
Overall Median Number of Days Patients Alive After Treatment
Calculated median number of days of survival (patients alive days after treatment).
Time frame: First Day of Treatment Until Death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NK Cells With or Without Total Body Irradiation | Overall Median Number of Days Patients Alive After Treatment | 124 Days |