Allogeneic Natural Killer (NK) Cells in Patients With Advanced Metastatic Breast Cancer

Phase 2

Terminated

• Conditions: Breast Cancer
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Other: Natural killer cell infusion; Biological: Interleukin-2

• Registration Number: NCT00376805
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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.

Study Timeline

• Study Start: 2006-04
• Study First Submitted: 2006-09-13
• Study First Submitted QC: 2006-09-13
• Study First Posted: 2006-09-15
• Primary Completion: 2009-09
• Study Completion: 2010-01
• Results First Submitted: 2010-07-13
• Results First Submitted QC: 2010-07-13
• Results First Posted: 2010-08-12
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-03
• Last Update Posted: 2017-12-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

Not provided

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Exclusion Criteria

• At least 3 days since prior prednisone or other immunosuppressive medications
• No other concurrent therapy for cancer

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All Treated Patients	Interleukin-2	All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.
All Treated Patients	Total body irradiation	All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.
All Treated Patients	Fludarabine	All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.
All Treated Patients	Natural killer cell infusion	All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.
All Treated Patients	Cyclophosphamide	All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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).

Trial Locations

Locations (1)

Masonic Cancer Center at University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States