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

NCT ID: NCT00376805

Last Updated: 2017-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2010-01-31

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; male breast cancer; recurrent breast cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All Treated Patients

All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

administered intravenously 25 mg/m\^2 times 5 doses

Cyclophosphamide

Intervention Type: DRUG

administered intravenously 60 mg/kg days times 2 doses.

Total body irradiation

Intervention Type: RADIATION

200 cGy (gray) on day -1

Natural killer cell infusion

Intervention Type: OTHER

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.

Interleukin-2

Intervention Type: BIOLOGICAL

administered subcutaneously (10 MU) 3 times per week for 6 doses

Interventions

Fludarabine

administered intravenously 25 mg/m\^2 times 5 doses

Intervention Type: DRUG

Cyclophosphamide

administered intravenously 60 mg/kg days times 2 doses.

Intervention Type: DRUG

Total body irradiation

200 cGy (gray) on day -1

Intervention Type: RADIATION

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.

Intervention Type: OTHER

Interleukin-2

administered subcutaneously (10 MU) 3 times per week for 6 doses

Intervention Type: BIOLOGICAL

Other Intervention Names

Fludara; Endoxan, Cytoxan, Neosar, Procytox; radiation; NK cells; IL-2

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Miller, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Sarah Cooley, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

UMN-0505M70037

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-MT2005-08

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-2005LS033

Identifier Type: -

Identifier Source: org_study_id

NCT00167193

Identifier Type: -

Identifier Source: nct_alias