Allogeneic Natural Killer (NK) Cells in Patients With Advanced Metastatic Breast Cancer
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.
Radiation: Total body irradiation
Other: Natural killer cell infusion
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Natural Killer Cells in Patients With Advanced Metastatic Breast Cancer|
- Number of Patients Who Had Expansion of Natural Killer Cells [ Time Frame: Day 14 ] [ Designated as safety issue: No ]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).
- Number of Patients by Disease Response [ Time Frame: 6 Months, 1 Year ] [ Designated as safety issue: No ]
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 [ Time Frame: Within 100 days, After 100 days ] [ Designated as safety issue: Yes ]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 [ Time Frame: First Day of Treatment Until Death ] [ Designated as safety issue: No ]Calculated median number of days of survival (patients alive days after treatment).
|Study Start Date:||April 2006|
|Study Completion Date:||January 2010|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
Experimental: All Treated Patients
All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.
administered intravenously 25 mg/m^2 times 5 doses
Other Name: FludaraDrug: Cyclophosphamide
administered intravenously 60 mg/kg days times 2 doses.
Other Name: Endoxan, Cytoxan, Neosar, ProcytoxRadiation: Total body irradiation
200 cGy (gray) on day -1
Other Name: radiationOther: Natural killer cell infusion
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.
Other Name: NK cellsBiological: Interleukin-2
administered subcutaneously (10 MU) 3 times per week for 6 doses
Other Name: IL-2
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00376805
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Study Chair:||Jeffrey Miller, MD||Masonic Cancer Center, University of Minnesota|
|Principal Investigator:||Sarah Cooley, MD||Masonic Cancer Center, University of Minnesota|